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Find video protocols related to scientific articles indexed in Pubmed.
Intake of freshwater fish and associated Fatty acids and risk of breast cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-09-2014
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To investigate the association between intake of freshwater fish and their fatty acids and the risk of breast cancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Total freshwater fish intake was linked to decrease in the adjusted OR for breast cancer, but without dose-dependence. Analyses by freshwater fish species showed that consumption of black carp and silver carp was inversely related to breast cancer risk, with adjusted-ORs for the highest intake category of black carp (?500g/month) of 0.54 (95%CI=0.33-0.92; P trend<0.002) and for silver carp (?1000g/month) of 0.19 (95%CI=0.11-0.33; P trend<0.001). In contrast, consumption of crucian carp was positively related to breast cancer risk, with an adjusted OR for the highest intake category (?1000g/month) of 6.09 (95%CI=3.04-12.2; P trend<0.001). Moderate intakes of SFA, PUFA, n3-PUFA and n6-PUFA from freshwater fish may decrease the risk of breast cancer among premenopausal women. The findings of this study suggest that intake of freshwater fish and their fatty acids may modify risk of breast cancer, and that different species of freshwater fish could have a different actions on breast cancer risk. Future epidemiologic studies are needed to know the effects of freshwater fish intake on breast cancer risk and the cause of these effects.
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Protective roles of aldo-keto reductase 1B10 and autophagy against toxicity induced by p-quinone metabolites of tert-butylhydroquinone in lung cancer A549 cells.
Chem. Biol. Interact.
PUBLISHED: 08-19-2014
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tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect at low doses, but is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (TBQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-tert-butyl-2,3-epoxy-4-benzoquinone (TBE). Both TBQ and TBE are cytotoxic, but their toxic mechanisms have not been fully characterized. In this study, we have investigated the toxic mechanisms of TBQ and TBE, and the defense system against the two p-quinones using lung cancer A549 cells. TBQ and TBE, but not BHQ and TBEH, showed cytotoxicity to A549 cells. Neither caspase-3 activation nor an increase in the expression of endoplasmic reticulum stress-associating target genes was observed. TBQ and TBE reacted with reduced glutathione, and significantly decreased the glutathione level in A549 cells, suggesting that the cytotoxicity of the p-quinones is caused by their high electrophilicity reacting with biomolecules. The A549 cells treated with the p-quinones also showed increased levels of autophagic vacuoles and LC3-II protein, which are specific autophagy markers. An autophagy inhibitor, 3-methyladenine (3MA), decreased the LC3-II production by the p-quinones, but enhanced the cytotoxicity induced by TBQ and TBE, suggesting that autophagy contributes to alleviating the p-quinone-triggered cytotoxicity. In addition, the TBE-induced cytotoxicity and autophagy activation in the cells were significantly suppressed by overexpression of aldo-keto reductase (AKR)1B10 that efficiently reduces TBE into TBEH, and was augmented by pretreatment with a potent AKR1B10 inhibitor, C1. The effects of 3MA and C1 on the TBE-induced cytotoxicity were additive. The data provides evidence for the first time that autophagy and AKR1B10 contribute to the defense system against the cytotoxicity caused by the electrophilic p-quinone metabolites of BHQ.
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Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.
Roger L Milne, Barbara Burwinkel, Kyriaki Michailidou, Jose-Ignacio Arias-Perez, M Pilar Zamora, Primitiva Menéndez-Rodríguez, David Hardisson, Marta Mendiola, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Joe Dennis, Qin Wang, Manjeet K Bolla, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk Schoemaker, Yon-Dschun Ko, Hiltrud Brauch, Ute Hamann, , Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Jingmei Li, Judith S Brand, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Diether Lambrechts, Gilian Peuteman, Marie-Rose Christiaens, Ann Smeets, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katazyna Durda, Mikael Hartman, Miao Hui, Wei Yen Lim, Ching Wan Chan, Federick Marme, Rongxi Yang, Peter Bugert, Annika Lindblom, Sara Margolin, Montserrat Garcia-Closas, Stephen J Chanock, Jolanta Lissowska, Jonine D Figueroa, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Maartje J Hooning, Mieke Kriege, Ans M W van den Ouweland, Linetta B Koppert, Olivia Fletcher, Nichola Johnson, Isabel Dos-Santos-Silva, Julian Peto, Wei Zheng, Sandra Deming-Halverson, Martha J Shrubsole, Jirong Long, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Angela Cox, Simon S Cross, Malcolm W R Reed, Marjanka K Schmidt, Annegien Broeks, Sten Cornelissen, Linde Braaf, Daehee Kang, Ji-Yeob Choi, Sue K Park, Dong-Young Noh, Jacques Simard, Martine Dumont, Mark S Goldberg, France Labrèche, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Paolo Radice, Paolo Peterlongo, Jacopo Azzollini, Monica Barile, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, John L Hopper, Daniel F Schmidt, Enes Makalic, Melissa C Southey, Soo Hwang Teo, Cheng Har Yip, Kavitta Sivanandan, Wan-Ting Tay, Chen-Yang Shen, Chia-Ni Hsiung, Jyh-Cherng Yu, Ming-Feng Hou, Pascal Guénel, Thérèse Truong, Marie Sanchez, Claire Mulot, William Blot, Qiuyin Cai, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Natalia Bogdanova, Thilo Dörk, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Ben Zhang, Fergus J Couch, Amanda E Toland, Drakoulis Yannoukakos, Suleeporn Sangrajrang, James McKay, Xianshu Wang, Janet E Olson, Celine Vachon, Kristen Purrington, Gianluca Severi, Laura Baglietto, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Kamila Czene, Mikael Eriksson, Keith Humphreys, Hatef Darabi, Shahana Ahmed, Mitul Shah, Paul D P Pharoah, Per Hall, Graham G Giles, Javier Benitez, Alison M Dunning, Georgia Chenevix-Trench, Douglas F Easton.
Hum. Mol. Genet.
PUBLISHED: 06-18-2014
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Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
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Cigarette smoke inhalation and risk of lung cancer: a case-control study in a large Japanese population.
Eur. J. Cancer Prev.
PUBLISHED: 06-10-2014
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Several studies have shown that cigarette smoke inhalation is associated with an increased risk of lung cancer (LC) in European populations. The aim of our study was to clarify the relationship between cigarette smoke inhalation and the risk of LC in a Japanese population. We carried out a large case-control study of cigarette smoking and the risk of LC in Japan. Cases were newly diagnosed patients with histologically confirmed LC (n=653). Controls (n=1281) included hospital controls (n=453) and community-based controls (n=828). Odds ratios (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression analysis, adjusted for basic confounding variables including age, sex, drinking status, fruit and vegetable intake, family history of LC, occupation, and years of education. Compared with never smokers, ORs for ever smokers who do not inhale cigarette smoke (noninhalation) and ever smokers who inhale cigarette smoke (inhalation) were 1.72 (95% CI: 1.15-2.59) and 3.28 (95% CI: 2.38-4.53), respectively, when adjusted for basic confounding variables. When the analysis was restricted to ever smokers, the OR adjusted for basic confounding factors and pack-year of the risk of LC in the inhalation group was significantly higher than that in the noninhalation group. OR for the inhalation group compared with the noninhalation group was 1.52 (95% CI: 1.06-2.18, P=0.021). A similar pattern was observed in subcategory analyses for adenocarcinoma, squamous cell carcinoma and small cell carcinoma, and other histological types, although without statistical significance. Our case-control study showed that inhalation of cigarette smoke is a significant risk for LC independent from pack-years in a Japanese population.
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Induction of aldo-keto reductases (AKR1C1 and AKR1C3) abolishes the efficacy of daunorubicin chemotherapy for leukemic U937 cells.
Anticancer Drugs
PUBLISHED: 04-19-2014
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Continuous exposure to daunorubicin (DNR) confers resistance against the drug-elicited lethality of leukemic cells and then reduces the remission rate. However, the detailed mechanisms involved in resistance development of leukemic cells to DNR remain unclear. Upregulation of aldo-keto reductases (AKRs) in human leukemic U937 cells was evaluated by gene-specific PCR and western blot analyses, and the contribution of AKRs toward the DNR sensitivity was assessed using gene expression and RNA-interference techniques and specific inhibitors. In addition, DNR reduction and cell differentiation were analyzed by fluorescence high-performance liquid chromatography and flow cytometry, respectively. Treatment with high doses of DNR triggered apoptotic induction of U937 cells through the production of reactive oxygen species (ROS) and a ROS-dependent mechanism. In contrast, DNR, at its sublethal doses, induced the expression of AKR1C1 and AKR1C3, both of which reduced the DNR sensitivity of the cells. The enzymes did not interfere with the cell differentiation caused by DNR, whereas their upregulation facilitated reduction of the anticancer drug and a ROS-derived lipid aldehyde 4-hydroxy-2-nonenal. These results suggest crucial roles of AKR1C1 and AKR1C3 in the acquisition of DNR resistance of leukemic cells by metabolizing both DNR and cytotoxic aldehydes derived from ROS-linked lipid peroxidation.
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Cloning and characterization of four rabbit aldo-keto reductases featuring broad substrate specificity for xenobiotic and endogenous carbonyl compounds: relationship with multiple forms of drug ketone reductases.
Drug Metab. Dispos.
PUBLISHED: 02-07-2014
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Multiple forms of reductases for several drug ketones were isolated from rabbit liver, but their interrelationship and physiologic roles remain unknown. We isolated cDNAs for four aldo-keto reductases (AKR1C30, AKR1C31, AKR1C32, and AKR1C33), which share high amino acid sequence identity with the partial sequences of two rabbit naloxone reductases. The four recombinant enzymes reduced a variety of carbonyl compounds, including endogenous ?-dicarbonyls (e.g., isatin and diacetyl), aldehydes (e.g., farnesal and 4-oxo-2-nonenal), and ketosteroids. They differed in specificity for drug ketones and ketosteroids. Although daunorubicin and befunolol were common substrates of all of the enzymes, AKR enzymes specifically reduced naloxone (AKR1C30, AKR1C32, and AKR1C33), metyrapone (AKR1C32 and AKR1C33), loxoprofen (AKR1C31 and AKR1C32), ketotifen (AKR1C30), and naltrexone and fenofibric acid (AKR1C33). AKR1C30 reduced only 17-keto-5?-androstanes, whereas the other enzymes were active toward 3-, 17-, and 20-ketosteroids, and AKR1C33 further reduced 3-keto groups of bile acids and 7?-hydroxy-5?-cholestanes. In addition, AKR1C30, AKR1C31, AKR1C32, and AKR1C33 were selectively inhibited by carbenoxolone, baccharin, phenolphthalein, and zearalenone, respectively. The mRNAs for the four enzymes were ubiquitously expressed in male rabbit tissues, in which highly expressed tissues were the brain, heart, liver, kidney, intestine, colon, and testis (for AKR1C30 and AKR1C31); brain, heart, liver, kidney, testis, lung, and adrenal gland (for AKR1C32); and liver and intestine (for AKR1C33). Thus, the four enzymes correspond to the multiple drug ketone reductases, and may function in the metabolisms of steroids, isatin and reactive carbonyl compounds, and bile acid synthesis.
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Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).
Int. J. Cancer
PUBLISHED: 01-30-2014
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While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.
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2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.
Jingmei Li, Linda S Lindström, Jia N Foo, Sajjad Rafiq, Marjanka K Schmidt, Paul D P Pharoah, Kyriaki Michailidou, Joe Dennis, Manjeet K Bolla, Qin Wang, Laura J van 't Veer, Sten Cornelissen, Emiel Rutgers, Melissa C Southey, Carmel Apicella, Gillian S Dite, John L Hopper, Peter A Fasching, Lothar Haeberle, Arif B Ekici, Matthias W Beckmann, Carl Blomqvist, Taru A Muranen, Kristiina Aittomäki, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, , Kelly-Anne Phillips, Sue-Anne McLachlan, Diether Lambrechts, Bernard Thienpont, Ann Smeets, Hans Wildiers, Jenny Chang-Claude, Dieter Flesch-Janys, Petra Seibold, Anja Rudolph, Graham G Giles, Laura Baglietto, Gianluca Severi, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Vessela Kristensen, Grethe I Grenaker Alnæs, Anne-Lise Borresen-Dale, Silje Nord, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert Tollenaar, Caroline Seynaeve, Maartje Hooning, Mieke Kriege, Antoinette Hollestelle, Ans van den Ouweland, Yi Li, Ute Hamann, Diana Torres, Hans U Ulmer, Thomas Rüdiger, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shou-Tung Chen, Soo Hwang Teo, Nur Aishah Mohd Taib, Cheng Har Yip, Gwo Fuang Ho, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Daehee Kang, Ji-Yeob Choi, Sue K Park, Keun-Young Yoo, Tom Maishman, William J Tapper, Alison Dunning, Mitul Shah, Robert Luben, Judith Brown, Chiea Chuen Khor, Diana M Eccles, Heli Nevanlinna, Douglas Easton, Keith Humphreys, Jianjun Liu, Per Hall, Kamila Czene.
Nat Commun
PUBLISHED: 01-28-2014
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Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
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Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10.
Toxicol. Appl. Pharmacol.
PUBLISHED: 01-23-2014
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Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 ?M elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-l-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling.
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Alcohol and dietary folate intake and the risk of breast cancer: a case-control study in Japan.
Eur. J. Cancer Prev.
PUBLISHED: 11-08-2013
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Owing to its interaction with alcohol, folate has been suggested to be a potential factor for many types of cancer. The impact of these factors on the risk of breast cancer among Asian populations has not been fully examined, however, particularly with respect to receptor status. We carried out a case-control study in premenopausal and postmenopausal Japanese women, including 1754 breast cancer patients and 3508 noncancer controls. We determined the association between self-reported alcohol drinking, dietary folate intake, and the risk of breast cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic models adjusted for potential confounders. Alcohol consumption was associated with the risk of breast cancer, with the OR for a drinker consuming 23 g or more per day relative to a nondrinker of 1.39 (95% CI: 1.07-1.80). A significant inverse association was observed between folate intake and overall risk of breast cancer, with an OR of 0.79 (95% CI: 0.68-0.93; Ptrend=0.004) for the highest tertile relative to the lowest. The OR of a drinker consuming 23 g or more per day relative to a nondrinker with a low folate intake was 1.58 (95% CI: 1.06-2.33). However, a significantly increased risk was not observed in tertile 2 and tertile 3 folate in taker with any amount of alcohol consumption. Higher folate intake decreases the risk of breast cancer among Japanese, whereas alcohol intake increases the risk. These two factors interact with each other, and the excess risk of breast cancer with alcohol consumption might be attenuated by increasing the intake of folate. In addition, the effects of folate/alcohol may vary according to the tumor subtype.
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Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women.
Int. J. Gynecol. Cancer
PUBLISHED: 11-01-2013
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Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer.
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Cigarette smoking and pancreatic cancer risk: a revisit with an assessment of the nicotine dependence phenotype.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-03-2013
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Cigarette smoking is a well-established risk factor of pancreatic cancer (PC). Although an association between nicotine dependence phenotype, namely time to first cigarette (TTFC) after waking, and the risk of several smoking-related cancers has been reported, an association between TTFC and PC risk has not been reported. We assessed the impact of smoking behavior, particularly TTFC, on PC risk in a Japanese population.
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Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan.
Int. J. Cancer
PUBLISHED: 07-17-2013
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The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk.
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Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D?, and other endogenous and xenobiotic carbonyl compounds.
Biochem. Pharmacol.
PUBLISHED: 06-27-2013
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3-Hydroxyhexobarbital dehydrogenase (3HBD) catalyzes NAD(P)?-linked oxidation of 3-hydroxyhexobarbital into 3-oxohexobarbital. The enzyme has been thought to act as a dehydrogenase for xenobiotic alcohols and some hydroxysteroids, but its physiological function remains unknown. We have purified rabbit 3HBD, isolated its cDNA, and examined its specificity for coenzymes and substrates, reaction directionality and tissue distribution. 3HBD is a member (AKR1C29) of the aldo-keto reductase (AKR) superfamily, and exhibited high preference for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D?, which were converted to 3?-, 17?- and 20?-hydroxysteroids and 9?,11?-prostaglandin F?, respectively. Especially, ?-diketones (such as isatin and diacetyl) and lipid peroxidation-derived aldehydes (such as 4-oxo- and 4-hydroxy-2-nonenals) were excellent substrates showing low K(m) values (0.1-5.9 ?M). In 3HBD-overexpressed cells, 3-oxohexobarbital and 5?-androstan-3?-ol-17-one were metabolized into 3-hydroxyhexobarbital and 5?-androstane-3?,17?-diol, respectively, but the reverse reactions did not proceed. The overexpression of the enzyme in the cells decreased the cytotoxicity of 4-oxo-2-nonenal. The mRNA for 3HBD was ubiquitously expressed in rabbit tissues. The results suggest that 3HBD is an NADPH-preferring reductase, and plays roles in the metabolisms of steroids, prostaglandin D?, carbohydrates and xenobiotics, as well as a defense system, protecting against reactive carbonyl compounds.
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Genome-wide association study of the genetic factors related to confectionery intake: Potential roles of the ADIPOQ gene.
Obesity (Silver Spring)
PUBLISHED: 05-29-2013
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Objective: The excessive consumption of confectionery might have adverse effects on human health. To screen genetic factors associated with confectionery-intake frequency, a genome-wide association study (GWAS) in Japan was conducted. Design and Methods: For the discovery phase (stage 1), we conducted a GWAS of 939 noncancer patients in a cancer hospital. Additive models were used to test associations between genotypes of approximately 500,000 single-nucleotide polymorphisms (SNPs) and the confectionery-intake score (based on intake frequency). We followed-up association signals with P < 1 × 10(-5) and minor allele frequency >0.01 in stage 1 by genotyping the SNPs of 4,491 participants in a cross-sectional study within a cohort (replication phase [stage 2]). Results: We identified 12 SNPs in stage 1 that were potentially related to confectionery intake. In stage 2, this association was replicated for one SNP (rs822396; P = 0.049 for stage 2 and 4.2 × 10(-5) for stage 1+2) in intron 1 of the ADIPOQ gene, which encodes the adipokine adiponectin. Conclusions: Given the biological plausibility and previous relevant findings, the association of an SNP in the ADIPOQ gene with a preference for confectionery is worthy of follow-up and provides a good working hypothesis for experimental testing.
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Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer.
Cancer Sci.
PUBLISHED: 05-10-2013
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In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk.
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Active and passive smoking, and alcohol drinking and breast cancer risk in chinese women.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-30-2013
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To evaluate the relation between smoking, alcohol drinking and risk of breast cancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The results revealed that smoking, whether active or passive through the husband, was related to increased risk of breast cancer. The ORs (adjusted for age, menopausal status, educational levels, occupation, body mass index and income) were 3.55 (95%CI: 1.27-9.91) for active smoking and 1.47 (95%CI: 1.18-1.84) for passive smoking from husbands, respectively. A significant positive relationship was observed between breast cancer risk and the degree of husbands smoking. There were significant increase trend in ORs with the daily smoked number of cigarettes of husbands, the passive smoking years from husbands and the pack-years of husbands smoking (trend test: p=0.00003, 0.00013 and 0.0001, respectively). Alcohol consumption was also found to be a risk factor. The findings of this study in particular suggest that husbands smoking increases risk of breast cancer in Chinese women.
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Polymorphisms in XRCC1 Gene, Alcohol drinking, and Risk of Colorectal Cancer: a Case-control Study in Jiangsu Province of China.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-09-2013
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To evaluate the relationship between alcohol drinking, XRCC1 codon 194 and 399 polymorphisms and risk of colorectal cancer, we conducted a case-control study with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. The XRCC1 codon 194 and 399 genotypes were identified using polymerase chain reaction and restrictrion fragment length polymorphism methods (PCR-RFLP). A structured questionnaire was used to elicit detailed information. Odds ratios (ORs) were estimated with an unconditional logistic model. In this study no significant differences were observed among the studied groups with regard to the genotype distribution of the XRCC1 codons 194 and 399 and the risk of colorectal cancer did not appear to be significantly influenced by genotype alone, whereas alcohol consumption showed a positive association (P for trend <0.01). When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake. These findings support the conclusion that colorectal cancer susceptibility may be altered by gene-environment interactions.
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The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer.
Carcinogenesis
PUBLISHED: 03-01-2013
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The impact of alcohol on the risk of stomach cancer is controversial. Although aldehyde dehydrogenase 2 (ALDH2) Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.28 (0.77-2.12) for those with ALDH2 Glu/Glu and 3.93 (1.99-5.79) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (P for interaction = 0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis.
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Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.
Stig E Bojesen, Karen A Pooley, Sharon E Johnatty, Jonathan Beesley, Kyriaki Michailidou, Jonathan P Tyrer, Stacey L Edwards, Hilda A Pickett, Howard C Shen, Chanel E Smart, Kristine M Hillman, Phuong L Mai, Kate Lawrenson, Michael D Stutz, Yi Lu, Rod Karevan, Nicholas Woods, Rebecca L Johnston, Juliet D French, Xiaoqing Chen, Maren Weischer, Sune F Nielsen, Melanie J Maranian, Maya Ghoussaini, Shahana Ahmed, Caroline Baynes, Manjeet K Bolla, Qin Wang, Joe Dennis, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Sue Healey, Michael Lush, Daniel C Tessier, Daniel Vincent, Françis Bacot, , Ignace Vergote, Sandrina Lambrechts, Evelyn Despierre, Harvey A Risch, Anna González-Neira, Mary Anne Rossing, Guillermo Pita, Jennifer A Doherty, Nuria Alvarez, Melissa C Larson, Brooke L Fridley, Nils Schoof, Jenny Chang-Claude, Mine S Cicek, Julian Peto, Kimberly R Kalli, Annegien Broeks, Sebastian M Armasu, Marjanka K Schmidt, Linde M Braaf, Boris Winterhoff, Heli Nevanlinna, Gottfried E Konecny, Diether Lambrechts, Lisa Rogmann, Pascal Guénel, Attila Teoman, Roger L Milne, Joaquín J García, Angela Cox, Vijayalakshmi Shridhar, Barbara Burwinkel, Frederik Marme, Rebecca Hein, Elinor J Sawyer, Christopher A Haiman, Shan Wang-Gohrke, Irene L Andrulis, Kirsten B Moysich, John L Hopper, Kunle Odunsi, Annika Lindblom, Graham G Giles, Hermann Brenner, Jacques Simard, Galina Lurie, Peter A Fasching, Michael E Carney, Paolo Radice, Lynne R Wilkens, Anthony Swerdlow, Marc T Goodman, Hiltrud Brauch, Montserrat Garcia-Closas, Peter Hillemanns, Robert Winqvist, Matthias Dürst, Peter Devilee, Ingo Runnebaum, Anna Jakubowska, Jan Lubiński, Arto Mannermaa, Ralf Bützow, Natalia V Bogdanova, Thilo Dörk, Liisa M Pelttari, Wei Zheng, Arto Leminen, Hoda Anton-Culver, Clareann H Bunker, Vessela Kristensen, Roberta B Ness, Kenneth Muir, Robert Edwards, Alfons Meindl, Florian Heitz, Keitaro Matsuo, Andreas du Bois, Anna H Wu, Philipp Harter, Soo-Hwang Teo, Ira Schwaab, Xiao-Ou Shu, William Blot, Satoyo Hosono, Daehee Kang, Toru Nakanishi, Mikael Hartman, Yasushi Yatabe, Ute Hamann, Beth Y Karlan, Suleeporn Sangrajrang, Susanne Krüger Kjaer, Valerie Gaborieau, Allan Jensen, Diana Eccles, Estrid Høgdall, Chen-Yang Shen, Judith Brown, Yin Ling Woo, Mitul Shah, Mat Adenan Noor Azmi, Robert Luben, Siti Zawiah Omar, Kamila Czene, Robert A Vierkant, Børge G Nordestgaard, Henrik Flyger, Celine Vachon, Janet E Olson, Xianshu Wang, Douglas A Levine, Anja Rudolph, Rachel Palmieri Weber, Dieter Flesch-Janys, Edwin Iversen, Stefan Nickels, Joellen M Schildkraut, Isabel dos Santos Silva, Daniel W Cramer, Lorna Gibson, Kathryn L Terry, Olivia Fletcher, Allison F Vitonis, C Ellen van der Schoot, Elizabeth M Poole, Frans B L Hogervorst, Shelley S Tworoger, Jianjun Liu, Elisa V Bandera, Jingmei Li, Sara H Olson, Keith Humphreys, Irene Orlow, Carl Blomqvist, Lorna Rodriguez-Rodriguez, Kristiina Aittomäki, Helga B Salvesen, Taru A Muranen, Elisabeth Wik, Barbara Brouwers, Camilla Krakstad, Els Wauters, Mari K Halle, Hans Wildiers, Lambertus A Kiemeney, Claire Mulot, Katja K Aben, Pierre Laurent-Puig, Anne Mvan Altena, Thérèse Truong, Leon F A G Massuger, Javier Benitez, Tanja Pejovic, Jose Ignacio Arias Perez, Maureen Hoatlin, M Pilar Zamora, Linda S Cook, Sabapathy P Balasubramanian, Linda E Kelemen, Andreas Schneeweiss, Nhu D Le, Christof Sohn, Angela Brooks-Wilson, Ian Tomlinson, Michael J Kerin, Nicola Miller, Cezary Cybulski, Brian E Henderson, Janusz Menkiszak, Fredrick Schumacher, Nicolas Wentzensen, Loic Le Marchand, Hannah P Yang, Anna Marie Mulligan, Gord Glendon, Svend Aage Engelholm, Julia A Knight, Claus K Høgdall, Carmel Apicella, Martin Gore, Helen Tsimiklis, Honglin Song, Melissa C Southey, Agnes Jager, Ans M Wvan den Ouweland, Robert Brown, John W M Martens, James M Flanagan, Mieke Kriege, James Paul, Sara Margolin, Nadeem Siddiqui, Gianluca Severi, Alice S Whittemore, Laura Baglietto, Valerie McGuire, Christa Stegmaier, Weiva Sieh, Heiko Muller, Volker Arndt, France Labrèche, Yu-Tang Gao, Mark S Goldberg, Gong Yang, Martine Dumont, John R McLaughlin, Arndt Hartmann, Arif B Ekici, Matthias W Beckmann, Catherine M Phelan, Michael P Lux, Jenny Permuth-Wey, Bernard Peissel, Thomas A Sellers, Filomena Ficarazzi, Monica Barile, Argyrios Ziogas, Alan Ashworth, Aleksandra Gentry-Maharaj, Michael Jones, Susan J Ramus, Nick Orr, Usha Menon, Celeste L Pearce, Thomas Brüning, Malcolm C Pike, Yon-Dschun Ko, Jolanta Lissowska, Jonine Figueroa, Jolanta Kupryjanczyk, Stephen J Chanock, Agnieszka Dansonka-Mieszkowska, Arja Jukkola-Vuorinen, Iwona K Rzepecka, Katri Pylkäs, Mariusz Bidzinski, Saila Kauppila, Antoinette Hollestelle, Caroline Seynaeve, Rob A E M Tollenaar, Katarzyna Durda, Katarzyna Jaworska, Jaana M Hartikainen, Veli-Matti Kosma, Vesa Kataja, Natalia N Antonenkova, Jirong Long, Martha Shrubsole, Sandra Deming-Halverson, Artitaya Lophatananon, Pornthep Siriwanarangsan, Sarah Stewart-Brown, Nina Ditsch, Peter Lichtner, Rita K Schmutzler, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Chiu-Chen Tseng, Daniel O Stram, David Van Den Berg, Cheng Har Yip, M Kamran Ikram, Yew-Ching Teh, Hui Cai, Wei Lu, Lisa B Signorello, Qiuyin Cai, Dong-Young Noh, Keun-Young Yoo, Hui Miao, Philip Tsau-Choong Iau, Yik Ying Teo, James McKay, Charles Shapiro, Foluso Ademuyiwa, George Fountzilas, Chia-Ni Hsiung, Jyh-Cherng Yu, Ming-Feng Hou, Catherine S Healey, Craig Luccarini, Susan Peock, Dominique Stoppa-Lyonnet, Paolo Peterlongo, Timothy R Rebbeck, Marion Piedmonte, Christian F Singer, Eitan Friedman, Mads Thomassen, Kenneth Offit, Thomas V O Hansen, Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Judy Garber, Steven A Narod, Jeffrey N Weitzel, Marco Montagna, Edith Olah, Andrew K Godwin, Drakoulis Yannoukakos, David E Goldgar, Trinidad Caldés, Evgeny N Imyanitov, Laima Tihomirova, Banu K Arun, Ian Campbell, Arjen R Mensenkamp, Christi J van Asperen, Kees E P van Roozendaal, Hanne Meijers-Heijboer, J Margriet Collée, Jan C Oosterwijk, Maartje J Hooning, Matti A Rookus, Rob B van der Luijt, Theo A Mvan Os, D Gareth Evans, Debra Frost, Elena Fineberg, Julian Barwell, Lisa Walker, M John Kennedy, Radka Platte, Rosemarie Davidson, Steve D Ellis, Trevor Cole, Brigitte Bressac-de Paillerets, Bruno Buecher, Francesca Damiola, Laurence Faivre, Marc Frénay, Olga M Sinilnikova, Olivier Caron, Sophie Giraud, Sylvie Mazoyer, Valérie Bonadona, Virginie Caux-Moncoutier, Aleksandra Toloczko-Grabarek, Jacek Gronwald, Tomasz Byrski, Amanda B Spurdle, Bernardo Bonanni, Daniela Zaffaroni, Giuseppe Giannini, Loris Bernard, Riccardo Dolcetti, Siranoush Manoukian, Norbert Arnold, Christoph Engel, Helmut Deissler, Kerstin Rhiem, Dieter Niederacher, Hansjoerg Plendl, Christian Sutter, Barbara Wappenschmidt, Ake Borg, Beatrice Melin, Johanna Rantala, Maria Soller, Katherine L Nathanson, Susan M Domchek, Gustavo C Rodriguez, Ritu Salani, Daphne Gschwantler Kaulich, Muy-Kheng Tea, Shani Shimon Paluch, Yael Laitman, Anne-Bine Skytte, Torben A Kruse, Uffe Birk Jensen, Mark Robson, Anne-Marie Gerdes, Bent Ejlertsen, Lenka Foretova, Sharon A Savage, Jenny Lester, Penny Soucy, Karoline B Kuchenbaecker, Curtis Olswold, Julie M Cunningham, Susan Slager, Vernon S Pankratz, Ed Dicks, Sunil R Lakhani, Fergus J Couch, Per Hall, Alvaro N A Monteiro, Simon A Gayther, Paul D P Pharoah, Roger R Reddel, Ellen L Goode, Mark H Greene, Douglas F Easton, Andrew Berchuck, Antonis C Antoniou, Georgia Chenevix-Trench, Alison M Dunning.
Nat. Genet.
PUBLISHED: 01-31-2013
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TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ?480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
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GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.
Paul D P Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke L Fridley, Jonathan P Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C Larson, Honglin Song, Daniel C Tessier, Francois Bacot, Daniel Vincent, Julie M Cunningham, Joe Dennis, Ed Dicks, , Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M Armasu, Laura Baglietto, Elisa V Bandera, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Ian Campbell, Michael E Carney, Renato S Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda S Cook, Daniel W Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David Fenstermacher, James Flanagan, Yu-Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Qi Guo, Mari K Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Høgdall, Claus K Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly R Kalli, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne Krüger Kjaer, Gottfried E Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubiński, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara Olson, Irene Orlow, James Paul, Tanja Pejovic, Liisa M Pelttari, Jenny Permuth-Wey, Malcolm C Pike, Elizabeth M Poole, Xiaotao Qu, Harvey A Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Gianluca Severi, Hui Shen, Vijayalakshmi Shridhar, Xiao-Ou Shu, Weiva Sieh, Melissa C Southey, Paul Spellman, Kazuo Tajima, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Agnieszka Timorek, Shelley S Tworoger, Anne M Van Altena, David Van Den Berg, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Elisabeth Wik, Boris Winterhoff, Yin Ling Woo, Anna H Wu, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Marc T Goodman, Per Hall, Douglas F Easton, Celeste L Pearce, Andrew Berchuck, Georgia Chenevix-Trench, Edwin Iversen, Alvaro N A Monteiro, Simon A Gayther, Joellen M Schildkraut, Thomas A Sellers.
Nat. Genet.
PUBLISHED: 01-30-2013
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Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
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Impact of PSCA variation on gastric ulcer susceptibility.
PLoS ONE
PUBLISHED: 01-01-2013
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Peptic ulcer is one of the most common gastrointestinal disorders with complex etiology. Recently we conducted the genome wide association study for duodenal ulcer and identified disease susceptibility variations at two genetic loci corresponding to the Prostate stem cell antigen (PSCA) gene and the ABO blood group (ABO) gene. Here we investigated the association of these variations with gastric ulcer in two Japanese case-control sample sets, a total of 4,291 gastric ulcer cases and 22,665 controls. As a result, a C-allele of rs2294008 at PSCA increased the risk of gastric ulcer with odds ratio (OR) of 1.13 (P value of 5.85×10(-7)) in an additive model. On the other hand, SNP rs505922 on ABO exhibited inconsistent result between two cohorts. Our finding implies presence of the common genetic variant in the pathogenesis of gastric and duodenal ulcers.
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Weight gain during adulthood and body weight at age 20 are associated with the risk of endometrial cancer in Japanese women.
J Epidemiol
PUBLISHED: 10-08-2011
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Current obesity is an established risk factor for endometrial cancer; however, the roles of weight gain during adulthood and obesity in early adulthood on endometrial cancer have not been elucidated. Here, we conducted a case-control study comprising 222 histologically diagnosed incident endometrial cancer cases and 2162 age- and menstrual-status matched non-cancer controls.
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A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population.
Breast Cancer Res. Treat.
PUBLISHED: 10-06-2011
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Genome-wide association studies (GWASs) have identified genetic variants associated with breast cancer. Most GWASs to date have been conducted in women of European descent, however, and the contribution of these variants as predictors in Japanese women is unknown. Here, we analyzed 23 genetic variants identified in previous GWASs and conducted a case-control study with 697 case subjects and 1,394 age- and menopausal status-matched controls. We fit conditional regression models with genetic variants and conventional risk factors. In addition, we created a polygenetic risk score, using those variants with a statistically significant association with breast cancer risk, and also evaluated the contribution of these genetic predictors using the c statistic. Eleven single-nucleotide polymorphisms (SNPs) revealed significant associations with breast cancer risk. A dose-dependent association was observed between the risk of breast cancer and the genetic risk score, which was an aggregate measure of alleles in seven selected variants, namely FGFR2-rs2981579, TOX3/TNRC9-rs3803662, C6orf97-rs2046210, 8q24-rs13281615, SLC4A7-rs4973768, LSP1-rs38137198, and CASP8-rs10931936. Compared to women with scores of 3 or less, odds ratios (ORs) for women with scores of 4-5, 6-7, 8-9, and 10 or more were 1.33 (95% confidence interval, 1.00-1.80), 1.71 (1.26-2.30), 3.01 (1.97-4.58), and 8.69 (2.75-27.5), respectively (P (trend) = 1.9 × 10(-9)). The c statistic for a model including the genetic risk score in addition to the conventional risk factors was 0.6933, versus 0.6652 with the conventional risk factors only (P = 1.3 × 10(-4)). Population-attributable fraction of the risk score was 33.0%. In conclusion, we identified a genetic risk predictor of breast cancer in a Japanese population. Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention.
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No association between angiotensin I converting enzyme (ACE) I/D polymorphism and gastric cancer risk among Japanese.
Nagoya J Med Sci
PUBLISHED: 09-21-2011
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The angiotensin I-converting enzyme (ACE) is involved in cell proliferation, angiogenesis, inflammation, and tissue remodeling, all of which could play a role in carcinogenesis. The DD genotype of ACE I/D polymorphism with a higher ACE level than either ID or II genotypes was reported to increase the risk of several cancers. This is a case-control study examining the association between the polymorphism and gastric cancer risks among Japanese. Cases numbered 583 patients aged 27 to 80 years with gastric cancer diagnosed at the Aichi Cancer Center Hospital from 2001 to 2005. Controls were 1,742 sex and age frequency-matched cancer-free patients, who visited the same hospital during that same period. The ACE I/D polymorphism was genotyped using a polymerase chain reaction with confronting two-pair primers. The results showed that the age- and sex- adjusted ORs of gastric cancer were 0.95 (95% CI, 0.78-1.16) for ID, and 1.08 (95% CI, 0.80-1.46) for DD relative to II. Among the controls with H. pylori sero-positive or gastric atrophy (GA), the ORs of ID and DD relative to II were 1.20 (95% CI, 0.88-1.63) and 1.16 (95% CI, 0.73-1.84) for mild GA, and 1.22 (95% CI, 0.84-1.78) and 1.08 (95% CI, 0.61-1.89) for severe GA, respectively. In conclusion, there was no significant association of the ACE I/D polymorphism with the risk of gastric cancer. Among the controls, the polymorphism was not associated with the severity of GA.
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Interaction between IGF-1 polymorphisms and overweight for the risk of pancreatic cancer in Japanese.
Int J Mol Epidemiol Genet
PUBLISHED: 09-19-2011
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Although several reports have described a possible association between insulin-like growth factors-1 (IGF-1) and pancreatic cancer (PC) risk, this association has not been evaluated in the non-Caucasian population. To assess the impact of IGF-1 polymorphisms on PC risk in Japanese, we conducted a case-control study which compared the frequency of ten single nucleotide polymorphisms (SNPs) and haplotypes of IGF-1. SNPs were investigated using the TaqMan method in 176 patients with PC and 1402 control subjects. Exposure to risk factors was assessed from the results of a self-administered questionnaire. Associations and gene-environment interactions were examined using an unconditional logistic regression model. We did not observe any significant main effect of IGF-1 loci, but did find interactions between rs5742714 and past and/or current body-mass index (BMI) status. Among patients with BMI > 25 at age 20, an increased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.048) and rs6214 (P = 0.043). Among patients with current BMI > 25, an increased or decreased PC risk was observed with the addition of the minor allele for rs5742714 (trend P = 0.046), rs4764887 (P = 0.031) and rs5742612 (P = 0.038). Haplotype analysis of IGF-1 showed a significant association among patients who were either or both previously or currently overweight. These findings suggest that IGF-1 polymorphisms may affect the development of PC in the Japanese population in combination with obesity. Further studies to confirm these findings are warranted.
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Association between insulin-like growth factor-1 polymorphisms and stomach cancer risk in a Japanese population.
Cancer Sci.
PUBLISHED: 09-19-2011
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The insulin-like growth factor (IGF) signaling system plays a central role in cellular growth, differentiation and proliferation. Although the association between IGF1 gene polymorphisms and cancer risk has been evaluated for several carcinomas, this association has not yet been examined for stomach cancer. We investigated the association between IGF1 polymorphisms and the risk of stomach cancer in a Japanese population. A total of 703 patients with stomach cancer and 1462 non-cancer control subjects were enrolled in this case-control study. Associations between polymorphisms of 10 IGF1 loci and the risk of stomach cancer were evaluated using odds ratios (OR) and 95% confidence intervals (CI) in multiple logistic regression models. We observed that the C allele in rs1520220 and the G allele in rs4764887 were significantly associated with stomach cancer risk in the per-allele model after adjusting for other risk factors (OR: 1.14 [95% CI: 1.00-1.30] and OR: 1.18 [95% CI: 1.02-1.36], respectively). We also observed a positive and dose-dependent association between the number of risk alleles and stomach cancer risk (P-trend: 0.019) when examining the two loci in the same model. These associations were still seen after adjusting for potential confounders, including sex, age, smoking status, history of diabetes and family history of stomach cancer. We did not find any significant interaction between these factors and the number of risk alleles. In conclusion, we observed a significant association between IGF1 polymorphisms and stomach cancer risk among a Japanese population. Examination of the biological significance of IGF1 is warranted.
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Interaction between CYP19A1 polymorphisms and body mass index in the risk of endometrial cancer in postmenopausal Japanese women.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-09-2011
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Extra-ovarian sex hormone production plays an important role in endometrial cancer in postmenopausal women. Aromatase, which is encoded by CYP19A1, is a key enzyme in estrogen biosynthesis after menopause. To examine the association between polymorphisms in CYP19A1 and endometrial cancer risk among postmenopausal Japanese women, we conducted a hospital-based case control study in 48 patients with histologically diagnosed incident endometrial cancer and 253 non-cancer control subjects. Information on lifestyle factors was obtained from a self-administered questionnaire. Twenty-five tag SNPs (single nucleotide polymorphisms) of CYP19A1 were examined by TaqMan methods and haplotype blocks were identified by LD analysis. Associations were assessed by an unconditional logistic regression model adjusted for potential confounders. We found no significant association between CYP19A1 genotypes and haplotypes and endometrial cancer risk. However, among women with a BMI (body mass index) >23, significantly positive associations were observed for rs2899473, rs1865803, rs16964220, rs2008691, rs17647707, rs17647719, rs1902586, rs936306, and rs1004982, while negative associations were seen for rs1902585, rs752760 and rs2445768. These showed significant interactions with BMI. Further, of the six haplotype blocks identified, the haplotype CTT of block 1, GATA of block 5 and CA of block 6 showed statistically significant interactions with BMI. These results suggest that CYP19A1 polymorphisms might play an important role in the etiology of endometrial cancer, and that the effect of these polymorphisms might be influenced by BMI.
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Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.
Hum. Mol. Genet.
PUBLISHED: 09-09-2011
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Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
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A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects.
Ann. Rheum. Dis.
PUBLISHED: 08-27-2011
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HLA-DRB1 is associated with rheumatoid arthritis (RA). However, it has recently been suggested that HLA-DRB1 is only associated with patients with RA who have anticitrullinated peptide/protein antibodies (ACPA), which are specific to RA.
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Impact of smoking status on clinical outcome in oral cavity cancer patients.
Oral Oncol.
PUBLISHED: 07-26-2011
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The association between smoking status and survival in oral cavity squamous cell carcinoma (OSCC) patients remains unclear. Therefore, we evaluated the association between smoking status before treatment and clinical outcome in OSCC patients. We conducted a retrospective cohort study of 222 OSCC patients who were treated at Aichi Cancer Center in Japan. Of these, 82 patients (36.9%) were non-smokers, 65 (29.3%) were light smokers (pack-years smoking (PY) <30), 54 (24.3%) were moderate smokers (30?PY<60), and 21 (9.5%) were heavy smokers (60?PY). The survival impact of pre-treatment smoking status was evaluated using multivariate proportional hazard models. Five-year overall survival for non-, light, moderate, and heavy smokers was 72.9% (95% confidence interval CI): (61.4-81.5), 85.5% (74.0-92.2), 59.9% (44.3-72.4) and 69.0% (42.8-85.0). Adjusted hazard ratios (HRs) for moderate and heavy smokers in comparison with light smokers were 2.44 (1.07-5.57, P=0.034) and 2.66 (0.97-7.33, P=0.058) and the dose-response relationship among smokers was statistically significance (P(trend)=0.024). In addition, adjusted HR for non-smokers relative to light smokers was 2.27 (0.84-6.15, P=0.108). We observed a suggestive heterogeneity in the impact of smoking status by treatment method (P for heterogeneity=0.069). Effect of smoking was evident only among the chemoradiotherapy or radiotherapy group. In this study, we found the significant positive dose-response relationship among smokers on clinical outcome in OSCC patients and that non-smokers were worse prognosis than light smokers. In addition, this effect might differ by treatment method.
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The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid carcinoma in the Japanese population.
J. Med. Genet.
PUBLISHED: 07-05-2011
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FOXE1 and NKX2-1 are two known genetic risk factors for the predisposition to sporadic papillary thyroid carcinoma (PTC) in Europeans, but their association in other ethnicities is still unknown.
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ABO genotype and the risk of gastric cancer, atrophic gastritis, and Helicobacter pylori infection.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-15-2011
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Although several studies have investigated the association between ABO blood type and risk of gastric cancer (GC), atrophic gastritis (AG), and Helicobacter pylori (HP) infection, no study has investigated these associations by using ABO genotype.
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Physiological, reproductive factors and breast cancer risk in Jiangsu province of China.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-02-2011
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To evaluate the relationship between physiological, reproductive factors and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as measures of risk for breast cancer. The results have revealed that there was an increasing risk of breast cancer, include early age at menarche(? 13 year), late age at menopause(< 50 year) and older age at first pregnancy (? 30 year). Breastfeeding was associated significantly with a reduced risk of breast cancer. Women who had history of breastfeeding were at significantly decreased OR (0.44, 95%CI: 0.27-0.73). The protective effects of breastfeeding for breast cancer seemed greater for women who had extended duration of breastfeeding during their lifetime (p for linear trend: 0.0095). These results suggested that physiological and reproductive factors may play important roles in the development of breast cancer among Jiangsu women of China.
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Selective inhibition of the tumor marker aldo-keto reductase family member 1B10 by oleanolic acid.
J. Nat. Prod.
PUBLISHED: 05-11-2011
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A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, was recently suggested as a therapeutic target in the treatment of several types of cancer. Due to its high sequence identity with human aldose reductase (AKR1B1), selective inhibition of AKR1B10 compared with AKR1B1 is required for the development of anticancer agents. In this study, we have examined AKR1B10 inhibition by seven pentacyclic triterpenes (1-7) that show potential anticancer properties. Among them, oleanolic acid (1) was found to be the most potent competitive inhibitor (inhibition constant, 72 nM) with the highest AKR1B10/AKR1B1 selectivity ratio of 1370. Molecular docking of 1 with AKR1B10 and AKR1B1 and site-directed mutagenesis studies suggested that the nonconserved residues Val301 and Gln303 in AKR1B10 are important for determining its inhibitory potency and selectivity. Oleanolic acid (1) also inhibited the cellular metabolism by AKR1B10 (IC(50), 4 ?M) and decreased mitomycin C tolerance of colon cancer HT29 cells. Thus, the selective and potent inhibition of AKR1B10 by 1 may be related to a possible cancer inhibitory role.
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Preparation of TiO2 thin films using octadecylamine Langmuir-Blodgett films and evaluation of their photocatalytic activity.
J Oleo Sci
PUBLISHED: 04-02-2011
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A study was conducted to demonstrate that nanometer-thick titanium dioxide (TiO(2)) thin films could be prepared by the hydrolysis of titanium potassium oxalate using octadecylamine (ODA) Langmuir-Blodgett (LB) films as templates. The amount of TiO(2) generated in the LB film was found to be proportional to the number of deposited ODA layers, which enables precise control of the TiO(2) film thickness. After heat treatment of the LB films at 300-600°C, the photocatalytic activities of the resulting TiO(2) films were determined from the decomposition of stearic acid cast films when irradiated with UV light for different time periods. Higher photocatalytic activity was observed in TiO(2) films heat treated at lower temperatures.
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Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
J Epidemiol
PUBLISHED: 03-30-2011
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Most diseases are thought to arise from interactions between environmental factors and the host genotype. To detect gene-environment interactions in the development of lifestyle-related diseases, and especially cancer, the Japan Multi-institutional Collaborative Cohort (J-MICC) Study was launched in 2005.
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Association between the SERPING1 gene and age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese.
PLoS ONE
PUBLISHED: 03-17-2011
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Recently, a complement component 1 inhibitor (SERPING1) gene polymorphism was identified as a novel risk factor for age-related macular degeneration (AMD) in Caucasians. We aimed to investigate whether variations in SERPING1 are associated with typical AMD or with polypoidal choroidal vasculopathy (PCV) in a Japanese population.
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ABO blood group alleles and the risk of pancreatic cancer in a Japanese population.
Cancer Sci.
PUBLISHED: 03-14-2011
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Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non-O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r(2) = 0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk.
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Genetic variants on chromosome 8q24 and colorectal neoplasia risk: a case-control study in China and a meta-analysis of the published literature.
PLoS ONE
PUBLISHED: 03-01-2011
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Previous studies have found that common genetic variants on chromosome 8q24 are associated with the risk of developing colorectal neoplasia. We conducted a hospital-based case-control study, including 435 cases and 788 unrelated controls to investigate the associations between common variants on 8q24 and the risk of colorectal cancer in a Chinese population. We also evaluated the association of rs6983267 with colorectal neoplasia in the published literature via a meta-analysis study. We found that rs6983267 was significantly associated with the risk of colorectal cancer in the Chinese population, with an adjusted odds-ratio (OR) for the GT heterozygotes and GG homozygotes of 1.30 (95% CI=?0.98-1.71, P?=?0.069) and 1.66 (95% CI?=?1.18-2.34, P?=?0.004), respectively, compared to the TT homozygotes, with a P-trend value of 0.003. No association was found for the other three loci (rs16901979, rs1447295 and rs7837688). In the meta-analysis of the published genetic association studies, the rs6983267 variant was found to be associated with an increased risk of colorectal neoplasia. The heterozygous GT carriers showed a 20% increased risk of colorectal neoplasia (OR=?1.20, 95% CI=?1.16-1.25; random effects model) with a summary OR for homozygous GG carriers of 1.39 (95% CI=?1.32-1.48; random effects model) compared to the TT genotype carriers. We found no significant differences between the association of rs6983267 and colorectal cancer and colorectal adenomas. In summary, our study confirms that the variant rs6983267 is a risk factor for colorectal neoplasia in various populations, including the Chinese population.
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Activation of aldo-keto reductase family member 1B14 (AKR1B14) by bile acids: Activation mechanism and bile acid-binding site.
Biochimie
PUBLISHED: 02-22-2011
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Aldo-keto reductase (AKR) 1B14, a rat ortholog of mouse androgen-dependent vas deferens protein (AKR1B7), is involved in the synthesis of prostaglandin F(2?) and detoxification of 4-oxononenal formed by lipid peroxidation. The NADPH-linked reductase activity of AKR1B14 was activated by various bile acids. Although the activation was increased by decreasing pH from 9.0 to 6.0, the concentrations giving maximum stimulation (2- to 18-fold) were 0.2-6.0 ?M for bile acids at pH 7.4. Kinetic analyses of the activation by glycochenodeoxycholic acid in the forward and reverse reactions, together with fluorescence changes and protection against 4-oxononenal-induced inactivation by bile acid, indicate that the bile acid binds to the enzyme and its coenzyme binary complex as a non-essential activator. The bile acid binding to AKR1B14 mainly accelerates the NADP(+) dissociation, the rate-limited step of the enzyme reaction. AKR1B7 was also activated by bile acids, but the activation was low and independent of pH. The mutagenesis of His269 and Leu267 of AKR1B14 into the corresponding residues (Arg and Pro, respectively) of AKR1B7 resulted in low and pH-independent activation by bile acids. The results, together with the docking of the bile acid in the recently determined crystal structure of AKR1B14, identify the bile acid-binding site of which His269 plays a key role in significant activation through its electrostatic interaction with the carboxyl group of bile acid, facilitating the release of NADP(+).
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An association between long-term exposure to ambient air pollution and mortality from lung cancer and respiratory diseases in Japan.
J Epidemiol
PUBLISHED: 02-12-2011
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Evidence for a link between long-term exposure to air pollution and lung cancer is limited to Western populations. In this prospective cohort study, we examined this association in a Japanese population.
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Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.
Cancer Res.
PUBLISHED: 02-08-2011
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We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10?³?], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10??], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region.
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Projected cancer mortality among Japanese males under different smoking prevalence scenarios: evidence for tobacco control goal setting.
Jpn. J. Clin. Oncol.
PUBLISHED: 01-24-2011
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Male smoking prevalence is still high in Japan, and quantitative information for tobacco control is scarce. The aim of the present study was to project cancer mortality among Japanese males under different future scenarios of smoking prevalence.
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Inverse association between toothbrushing and upper aerodigestive tract cancer risk in a Japanese population.
Head Neck
PUBLISHED: 01-21-2011
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Oral hygiene is attracting increasing attention as a potential risk factor for cancers. To investigate the association between toothbrushing frequency and upper aerodigestive tract (UADT) cancer, the authors conducted a large-scale case-control study.
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Ethnoepidemiology of HTLV-1 related diseases: ethnic determinants of HTLV-1 susceptibility and its worldwide dispersal.
Cancer Sci.
PUBLISHED: 01-06-2011
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Human T-cell lymphotropic virus type 1 is vertically transmitted in neonatal life and is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in adults. Persistence of HTLV-1 in host T cells, clonal expansion of the HTLV-1 carrying T cells, and emergence of malignantly transformed T cells are in accord with the multistep model of human cancer and roles for continuous interaction between host genes and environmental factors. This article reviews two lines of HTLV-1 investigation, one regarding worldwide surveillance of HTLV-1 infection foci by serological testing and molecular analysis of HTLV-1 isolates, and the other focusing on genetics of the human leukocyte antigen (HLA) that determines the ethnic background of HTLV-1 permissiveness and susceptibility to ATL or HAM/TSP. The serological surveillance revealed transcontinental dispersal of HTLV-1 in the prehistoric era that started out of Africa, spread to Austro-Melanesia and the Asian continent, then moved to North America and through to the southern edge of South America. This was highlighted by an Andean mummy study that proved ancient migration of paleo-mongoloid HTLV-1 from Asia to South America. Phylogenetic analysis of HLA alleles provided a basis for ethnic susceptibility to HTLV-1 infection and associated diseases, both ATL and HAM/TSP. Ethnicity-based sampling of peripheral blood lymphocytes has great potential for genome-wide association studies to illuminate ethnically defined host factors for viral oncogenesis with reference to HTLV-1 and other pathogenic elements causatively associated with chronic disease and malignancies.
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Rat aldose reductase-like protein (AKR1B14) efficiently reduces the lipid peroxidation product 4-oxo-2-nonenal.
Biol. Pharm. Bull.
PUBLISHED: 11-05-2010
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In this study, we examined the substrate specificity, inhibitor sensitivity and kinetic mechanism of a rat aldose reductase-like protein, which is named AKR1B14 in the aldo-keto reductase (AKR) superfamily. AKR1B14 catalyzed the nicotinamide adenine dinucleotide phosphate reduced form (NADPH)-dependent reduction of carbonyl compounds (derived from lipid peroxidation and glycation), xenobiotic aromatic aldehydes and some aromatic ketones. 4-Oxo-2-nonenal, the best substrate showing a K(m) value of 0.16 µM, was reduced into less reactive 4-oxo-2-nonenol, and its cytotoxicity was attenuated by the overexpression of the enzyme in cultured cells. The enzyme also showed low K(m) values (0.9-10 µM) for medium-chain aliphatic aldehydes (such as 4-hydroxynonenal, 1-hexenal and farnesal) and 3-deoxyglucosone, although the K(m) values for short-chain substrates (such as isocaproaldehyde, acrolein and methylglyoxal) were high (16-600 µM). In the reverse reaction, aliphatic and aromatic alcohols were oxidized by AKR1B14 at low rates. AKR1B14 was inhibited by aldose reductase inhibitors such as tolrestat and epalrestat, and their inhibition patterns were noncompetitive versus the aldehyde substrate and competitive with respect to the alcohol substrate. Kinetic analyses of the oxidoreduction and dead-end inhibition suggest that the reaction follows an ordered sequential mechanism.
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Smoking behavior and risk of Helicobacter pylori infection, gastric atrophy and gastric cancer in Japanese.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-03-2010
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Although many studies have shown that smoking is an established risk factor for gastric cancer, relatively few studies have investigated on which step smoking has effects in Helicobacter pylori (H. pylori) related gastric carcinogenesis. In this study we investigated the association of smoking with risk of three steps leading to gastric cancer: H. pylori infection, gastric atrophy, and gastric cancer. Among the participants who visited Aichi Cancer Center Hospital from year 2001 to 2005, 583 cases diagnosed as gastric cancer and age-and sex-frequency-matched 1,742 cancer free controls were sampled, from whom those without serum samples or without information about smoking habit were excluded, leaving 576 cases and 1,599 controls eligible for the analyses. Anti- H. pylori IgG antibody and serum pepsinogens (PG) were measured to detect H. pylori infection and gastric atrophy. Smoking status was asked by a self-administered questionnaire. The odds ratio (OR) of H. pylori infection, as well as the OR of gastric atrophy among the H. pylori seropositive controls was not significant for smokers. The age- and sex-adjusted OR of gastric cancer was significantly elevated relative to the subjects with gastric atrophy: OR=1.62 (95% confidence interval (CI), 1.19-2.22; P=0.002) for ever smokers and 2.52 (1.75-3.64; P<0.001) for current smokers, relative to never smokers. This study revealed that smoking behavior contributed to the increased risk of gastric carcinogenesis from gastric atrophy, and had little influence on H. pylori infection or gastric atrophy development.
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Effects of genetic polymorphisms in the ABCB1 gene on clinical outcomes in patients with gastric cancer treated by second-line chemotherapy.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-17-2010
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Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agents due to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encoded by the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated the effect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was to evaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advanced gastric cancer (AGC) treated with second-line chemotherapy.
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Smoking behavior and risk of helicobacter pylori infection, gastric atrophy and gastric cancer in Japanese.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-17-2010
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Although many studies have shown that smoking is an established risk factor for gastric cancer, relatively few studies have investigated on which step smoking has effects in Helicobacter pylori (H. pylori) related gastric carcinogenesis. In this study we investigated the association of smoking with risk of three steps leading to gastric cancer: H. pylori infection, gastric atrophy, and gastric cancer. Among the participants who visited Aichi Cancer Center Hospital from year 2001 to 2005, 583 cases diagnosed as gastric cancer and age-and sex-frequency-matched 1,742 cancer free controls were sampled, from whom those without serum samples or without information about smoking habit were excluded, leaving 576 cases and 1,599 controls eligible for the analyses. Anti- H. pylori IgG antibody and serum pepsinogens (PG) were measured to detect H. pylori infection and gastric atrophy. Smoking status was asked by a self-administered questionnaire. The odds ratio (OR) of H. pylori infection, as well as the OR of gastric atrophy among the H. pylori seropositive controls was not significant for smokers. The age- and sex-adjusted OR of gastric cancer was significantly elevated relative to the subjects with gastric atrophy: OR=1.62 (95% confidence interval (CI), 1.19-2.22; P=0.002) for ever smokers and 2.52 (1.75-3.64; P<0.001) for current smokers, relative to never smokers. This study revealed that smoking behavior contributed to the increased risk of gastric carcinogenesis from gastric atrophy, but had little influence on H. pylori infection or gastric atrophy development.
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Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis.
Rheumatology (Oxford)
PUBLISHED: 09-09-2010
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ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion.
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Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol.
Chem. Biol. Interact.
PUBLISHED: 08-20-2010
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Farnesol (FOH) and geranylgeraniol (GGOH) with multiple biological actions are produced from the mevalonate pathway, and catabolized into farnesoic acid and geranylgeranoic acid, respectively, via the aldehyde intermediates (farnesal and geranylgeranial). We investigated the intracellular distribution, sequences and properties of the oxidoreductases responsible for the metabolic steps in rat tissues. The oxidation of FOH and GGOH into their aldehyde intermediates were mainly mediated by alcohol dehydrogenases 1 (in the liver and colon) and 7 (in the stomach and lung), and the subsequent step into the carboxylic acids was catalyzed by a microsomal aldehyde dehydrogenase. In addition, high reductase activity catalyzing the aldehyde intermediates into FOH (or GGOH) was detected in the cytosols of the extra-hepatic tissues, where the major reductase was identified as aldo-keto reductase (AKR) 1C15. Human reductases with similar specificity were identified as AKR1B10 and AKR1C3, which most efficiently reduced farnesal and geranylgeranial among seven enzymes in the AKR1A-1C subfamilies. The overall metabolism from FOH to farnesoic acid in cultured cells was significantly decreased by overexpression of AKR1C15, and increased by addition of AKR1C3 inhibitors, tolfenamic acid and R-flurbiprofen. Thus, AKRs (1C15 in rats, and 1B10 and 1C3 in humans) may play an important role in controlling the bioavailability of FOH and GGOH.
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Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 08-04-2010
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To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking.
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PRKCH gene polymorphism is associated with the risk of severe gastric atrophy.
Gastric Cancer
PUBLISHED: 07-03-2010
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Individuals infected with Helicobacter pylori do not necessarily develop gastric atrophy (GA) and gastric cancer (GC). Several factors, including genetic polymorphism, can regulate the development of GA and GC. A G/A single nucleotide polymorphism (rs3783799) of the PRKCH gene, which encodes the eta isozyme of protein kinase C (PKCeta), has been reported to be a tag single nucleotide polymorphism (SNP) of the PRKCH gene linked to a functional 1425G/A SNP in exon 9 (rs2230500). To elucidate its applicability in the development of GA and GC, this study aimed to investigate the associations of the PRKCH polymorphism with the risks of GA and GC.
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Relationship of sFas with metabolic risk factors and their clusters.
Eur. J. Clin. Invest.
PUBLISHED: 06-30-2010
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Metabolic risk factors are known to cause atherosclerosis through inflammation. In the process of inflammation, soluble Fas (sFas) may interfere with the apoptotic pathway and contribute to dysregulated inflammation. Recent studies suggest sFas as a marker of inflammation in patients with cardiovascular diseases. However, whether a relationship exists between sFas levels and metabolic risk factors among healthy subjects remains unclear.
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Properties and tissue distribution of a novel aldo-keto reductase encoding in a rat gene (Akr1b10).
Arch. Biochem. Biophys.
PUBLISHED: 06-23-2010
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A recent rat genomic sequencing predicts a gene Akr1b10 that encodes a protein with 83% sequence similarity to human aldo-keto reductase (AKR) 1B10. In this study, we isolated the cDNA for the rat AKR1B10 (R1B10) from rat brain, and examined the enzymatic properties of the recombinant protein. R1B10 utilized NADPH as the preferable coenzyme, and reduced various aldehydes (including cytotoxic 4-hydroxy-2-hexenal and 4-hydroxy- and 4-oxo-2-nonenals) and ?-dicarbonyl compounds (such as methylglyoxal and 3-deoxyglucosone), showing low K(m) values of 0.8-6.1?M and 3.7-67?M, respectively. The enzyme also reduced glyceraldehyde and tetroses (K(m)=96-390?M), although hexoses and pentoses were inactive and poor substrates, respectively. Among the substrates, 4-oxo-2-nonenal was most efficiently reduced into 4-oxo-2-nonenol, and its cytotoxicity against bovine endothelial cells was decreased by the overexpression of R1B10. R1B10 showed low sensitivity to aldose reductase inhibitors, and was activated to approximately two folds by valproic acid, and alicyclic and aromatic carboxylic acids. The mRNA for R1B10 was expressed highly in rat brain and heart, and at low levels in other rat tissues and skin fibroblasts. The results suggest that R1B10 functions as a defense system against oxidative stress and glycation in rat tissues.
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CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-23-2010
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To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP).
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Cancer epidemiology and control in north-East Asia - past, present and future.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-18-2010
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China, Mongolia, Korea and Japan constitute North-East Asia. For reasons of largely shared ethnicity and culture, with various degress of mixed Chinese and Altaic elements, as well as geographical contiguity, they can be usefully grouped together for studies of chronic disease prevalence and particularly cancer. The fact of problems shared in common, with increasing disease rates, underlines the necessity for a coordinated approach to research and development of control measures. To provide a knowledge base, the present review of cancer registration and epidemiology data was conducted. The most frequent cancers in males of North-East Asia are in the lung, liver and stomach, with considerable geographical and temporal variation in their respective prevalences. However, colorectal cancer is also of increasing importance. In females the breast, together with the lung in China, the liver in Mongolia and the stomach in Korea and Japan, are most frequent. Variation in risk factors depends to a large extent on the local level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control.
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Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.
J. Natl. Cancer Inst.
PUBLISHED: 06-14-2010
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Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.
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HLA-A alleles and the risk of cervical squamous cell carcinoma in Japanese women.
J Epidemiol
PUBLISHED: 05-22-2010
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We conducted a case-control study to examine the relationship between human leukocyte antigen-A (HLA-A) allele polymorphism and the pathogenesis of cervical neoplasia among Japanese women.
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Selective inhibition of the tumor marker AKR1B10 by antiinflammatory N-phenylanthranilic acids and glycyrrhetic acid.
Biol. Pharm. Bull.
PUBLISHED: 05-13-2010
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A human aldose reductase-like protein, AKR1B10 in the aldo-keto reductase (AKR) superfamily, was recently identified as a tumor marker of several types of cancer. Tolrestat, an aldose reductase inhibitor (ARI), is known to be the most potent inhibitor of the enzyme. In this study, we compared the inhibitory effects of other ARIs including flavonoids on AKR1B10 and aldose reductase to evaluate their specificity. However, ARIs showed lower inhibitory potency for AKR1B10 than for aldose reductase. In the search for potent and selective inhibitors of AKR1B10 from other drugs used clinically, we found that non-steroidal antiinflammatory N-phenylanthranilic acids, diclofenac and glycyrrhetic acid competitively inhibited AKR1B10, showing K(i) values of 0.35-2.9 microM and high selectivity to this enzyme (43-57 fold versus aldose reductase). Molecular docking studies of mefenamic acid and glycyrrhetic acid in the AKR1B10-nicotinamide adenine dinucleotide phosphate (NADP(+)) complex and site-directed mutagenesis of the putative binding residues suggest that the side chain of Val301 and a hydrogen-bonding network among residues Val301, Gln114 and Ser304 are important for determining the inhibitory potency and selectivity of the non-steroidal antiinflammatory drugs. Thus, the potent and selective inhibition may be related to the cancer chemopreventive roles of the drugs, and their structural features may facilitate the design of new anti-cancer agents targeting AKR1B10.
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A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22, determines susceptibility to diffuse-type gastric cancer.
Gastroenterology
PUBLISHED: 05-08-2010
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Two major types of gastric cancer, intestinal and diffuse, develop through distinct mechanisms; the diffuse type is considered to be more influenced by genetic factors, although the mechanism is unknown. Our previous genome-wide association study associated 3 single nucleotide polymorphisms (SNPs) with diffuse-type gastric cancer (DGC); 1 was a functional SNP (rs2294008) in prostate stem cell antigen (PSCA), but the loci of the other 2 were not investigated.
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Folate intake along with genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase in patients with advanced gastric cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-08-2010
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A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.
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Comparison between self-reported facial flushing after alcohol consumption and ALDH2 Glu504Lys polymorphism for risk of upper aerodigestive tract cancer in a Japanese population.
Cancer Sci.
PUBLISHED: 04-23-2010
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Some Japanese exhibit facial flushing after drinking alcohol. Facial flushing was considered to be caused by acetaldehydemia. The concentration of blood acetaldehyde was concerned with the catalytic activity of acetaldehyde dehydrogenase (ALDH). Acetaldehyde dehydrogenase (ALDH)-2 polymorphism (rs671, Glu504Lys) was known to be associated with upper aerodigestive tract (UAT) cancer due to modulation of ALDH2 enzyme activity. It remains controversial whether facial flushing is useful in predicting UAT cancer risk as a surrogate marker of ALDH2 polymorphism. We conducted a case-control study to assess the risk of UAT cancer and facial flushing and ALDH2 polymorphism. Cases and controls were 585 UAT cancer patients and matched 1170 noncancer outpatients of Aichi Cancer Center Hospital. Information on facial flushing and other lifestyle factors was collected via a self-administered questionnaire. Association between facial flushing, polymorphism, and UAT cancer was assessed by odds ratios and 95% confidence intervals by using conditional logistic regression models. The facial flushing had no significant association with UAT cancer, although ALDH2 Lys allele was significantly associated with UAT cancer. No significant interaction between facial flushing and alcohol consumption was observed in this study, whereas ALDH2 Lys allele had significant association with UAT cancer. The misclassification between facial flushing and ALDH2 genotype was observed in 18% of controls with ALDH2 Glu/Glu genotype and in 16% of controls with ALDH2 Glu/Lys genotype. Facial flushing was less useful to predict UAT cancer risk than genotyping ALDH2 polymorphism.
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No association between AICDA 7888 C/T polymorphism, Helicobacter pylori seropositivity, and the risk of atrophic gastritis and gastric cancer in Japanese.
Gastric Cancer
PUBLISHED: 04-07-2010
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The aberrant expression of activation-induced cytidine deaminase (AICDA) was reportedly induced in gastric epithelial cells infected with cytotoxin-associated gene A (cagA)-positive Helicobacter pylori, resulting in the accumulation of alterations in the TP53 tumor suppressor gene in gastric cells. We investigated the association of the AICDA 7888 C/T polymorphism with H. pylori infection and the risk of gastric cancer and atrophic gastritis in Japanese subjects.
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Relationship between growth hormone 1 genetic polymorphism and susceptibility to colorectal cancer.
J. Hum. Genet.
PUBLISHED: 02-19-2010
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The aim of this study was to evaluate the relationship between smoking, alcohol drinking and genetic polymorphism of the growth hormone 1 gene (GH1) T1663A with reference to colorectal cancer. We conducted a case-control study with 315 cases of colorectal cancer and 438 population-based controls in the Jiangsu Province, China. GH1 T1663A genotypes were identified using PCR-RFLP (restriction fragment length polymorphism) methods. Information on smoking and drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The distribution of T/T and A/A genotypes was significantly different between controls and cases (chi(2)(MH)=3.877, P=0.049). Compared with the GH1 T/T genotype, the A/A genotype was at a decreased risk of developing colorectal cancer (sex-, age-, body mass index-, smoking- and alcohol drinking-adjusted OR=0.56, 95% confidence interval: 0.34-0.90). Smoking was not associated with the risk of colorectal cancer, whereas alcohol drinking was associated with an increased risk of colorectal cancer. Among nonsmokers or nondrinkers, individuals who had the GH1 A/A genotype were at a decreased risk of developing colorectal cancer compared with individuals who had the GH1 T allele. These results show that the GH1 T1663A A/A genotype can decrease the risk for colorectal cancer.
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No associations of Toll-like receptor 2 (TLR2) -196 to -174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese.
Gastric Cancer
PUBLISHED: 02-05-2010
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Recently, the association between gastric cancer risk and a functional polymorphism of Toll-like receptor 2 (TLR2), -196 to -174del, was reported for a Japanese population. This study aimed to confirm the associations of the polymorphism with the risk of gastric cancer, as well as Helicobacter pylori seropositivity and the risk of gastric atrophy in Japanese.
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Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
PLoS Genet.
PUBLISHED: 02-01-2010
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Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.