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Find video protocols related to scientific articles indexed in Pubmed.
Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study.
BMJ Open
PUBLISHED: 11-13-2014
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To explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population.
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Dietary intake of acrylamide and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-11-2014
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Acrylamide, classified in 1994 by IARC as 'probably carcinogenic' to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results, and could not further examine histological subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) sub-cohort of women (n=325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method, and was evaluated both as a continuous variable (per 10µg/day) and in quintiles; when subgroups by histological EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 ?g/day. No associations, and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10µg/day:1.02, 95%CI:0.96-1.09; HRQ5vsQ1:0.97, 95%CI:0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
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Carbohydrate intake in the etiology of Crohn's disease and ulcerative colitis.
Inflamm. Bowel Dis.
PUBLISHED: 09-30-2014
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Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC).
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Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study.
Am. J. Clin. Nutr.
PUBLISHED: 09-17-2014
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Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain.
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Circulating 25-Hydroxyvitamin D3 in Relation to Renal Cell Carcinoma Incidence and Survival in the EPIC Cohort.
Am. J. Epidemiol.
PUBLISHED: 09-08-2014
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Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)(2)), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases.
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Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: A nested case-control study: Plasma micronutrients and pancreatic cancer risk.
Int. J. Cancer
PUBLISHED: 08-30-2014
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Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (?- and ?-carotene, lycopene, ?-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), ?- and ?-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma ?-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend?=?0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend?=?0.06) and ?-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend?=?0.08. For ?- and ?-carotene, lutein, sum of carotenoids and ?-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of ?-carotene, zeaxanthin and ?-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.
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Distribution of lipid parameters according to different socio-economic indicators- the EPIC-Norfolk prospective population study.
BMC Public Health
PUBLISHED: 08-28-2014
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Data on the relationship between plasma levels of cholesterol and triglycerides and social class have been inconsistent. Most previous studies have used one classification of social class.
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Fruit and vegetable intake and cause-specific mortality in the EPIC study.
Eur. J. Epidemiol.
PUBLISHED: 08-26-2014
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Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95% confidence intervals (95% CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95% CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95% CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95% CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.
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Cod liver oil supplement consumption and health: cross-sectional results from the EPIC-Norfolk cohort study.
Nutrients
PUBLISHED: 08-22-2014
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Supplement users (SU) make healthy lifestyle choices; on the other hand, SU report more medical conditions. We hypothesised that cod liver oil (CLO) consumers are similar to non-supplement users, since CLO use might originate from historical motives, i.e., rickets prevention, and not health consciousness. CLO consumers were studied in order to identify possible confounders, such as confounding by indication. The European Prospective Investigation into Cancer (EPIC) investigates causes of chronic disease. The participants were 25,639 men and women, aged 40-79 years, recruited from general practices in Norfolk, East-Anglia (UK). Participants completed questionnaires and a health examination between 1993 and 1998. Supplement use was measured using 7-day diet diaries. CLO was the most common supplement used, more prevalent among women and associated with not smoking, higher physical activity level and more favourable eating habits. SU had a higher occurrence of benign growths and bone-related diseases, but CLO was negatively associated with cardiovascular-related conditions. Although the results of SU characteristics in EPIC-Norfolk are comparable with studies worldwide, the CLO group is different from SU in general. Confounding by indication takes place and will need to be taken into account when analysing prospective associations of CLO use with fracture risk and cardiovascular diseases.
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition.
Cancer Epidemiol
PUBLISHED: 08-22-2014
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There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n=1095) and borderline (n=96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR=1.22, 95% CI=1.02-1.48, P(trend)=0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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Impact of abdominal obesity and systemic hypertension on risk of coronary heart disease in men and women: the EPIC-Norfolk Population Study.
J. Hypertens.
PUBLISHED: 08-08-2014
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The objective of our study was to determine the respective contributions of waist circumference and systemic hypertension (HTN) to coronary heart disease (CHD) risk in a large population-based cohort representative of a contemporary European population.
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FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals.
Qibin Qi, Tuomas O Kilpeläinen, Mary K Downer, Toshiko Tanaka, Caren E Smith, Ivonne Sluijs, Emily Sonestedt, Audrey Y Chu, Frida Renstrom, Xiaochen Lin, Lars H Angquist, Jinyan Huang, Zhonghua Liu, Yanping Li, Muhammad Asif Ali, Min Xu, Tarunveer Singh Ahluwalia, Jolanda M A Boer, Peng Chen, Makoto Daimon, Johan Eriksson, Markus Perola, Yechiel Friedlander, Yu-Tang Gao, Denise H M Heppe, John W Holloway, Denise K Houston, Stavroula Kanoni, Yu-Mi Kim, Maarit A Laaksonen, Tiina Jääskeläinen, Nanette R Lee, Terho Lehtimäki, Rozenn N Lemaitre, Wei Lu, Robert N Luben, Ani Manichaikul, Satu Mannisto, Pedro Marques-Vidal, Keri L Monda, Julius S Ngwa, Louis Pérusse, Frank J A van Rooij, Yong-Bing Xiang, Wanqing Wen, Mary K Wojczynski, Jingwen Zhu, Ingrid B Borecki, Claude Bouchard, Qiuyin Cai, Cyrus Cooper, George V Dedoussis, Panos Deloukas, Luigi Ferrucci, Nita G Forouhi, Torben Hansen, Lene Christiansen, Albert Hofman, Ingegerd Johansson, Torben Jørgensen, Shigeru Karasawa, Kay-Tee Khaw, Mi-Kyung Kim, Kati Kristiansson, Huaixing Li, Xu Lin, Yongmei Liu, Kurt K Lohman, Jirong Long, Vera Mikkilä, Dariush Mozaffarian, Kari North, Oluf Pedersen, Olli Raitakari, Harri Rissanen, Jaakko Tuomilehto, Yvonne T van der Schouw, André G Uitterlinden, M Carola Zillikens, Oscar H Franco, E Shyong Tai, Xiao Ou Shu, David S Siscovick, Ulla Toft, W M Monique Verschuren, Peter Vollenweider, Nicholas J Wareham, Jacqueline C M Witteman, Wei Zheng, Paul M Ridker, Jae H Kang, Liming Liang, Majken K Jensen, Gary C Curhan, Louis R Pasquale, David J Hunter, Karen L Mohlke, Matti Uusitupa, L Adrienne Cupples, Tuomo Rankinen, Marju Orho-Melander, Tao Wang, Daniel I Chasman, Paul W Franks, Thorkild I A Sørensen, Frank B Hu, Ruth J F Loos, Jennifer A Nettleton, Lu Qi.
Hum. Mol. Genet.
PUBLISHED: 08-07-2014
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FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-07-2014
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Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting.
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Opposites don't attract: high spouse concordance for dietary supplement use in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.
Public Health Nutr
PUBLISHED: 07-31-2014
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Dietary supplements are commonly consumed but may not be beneficial for everyone. It is known that supplement users have healthy behaviour characteristics but until now concordance between spouses living in the same household has not been investigated and concordance may be an important behavioural determinant.
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Performance of the CHARGE-AF risk model for incident atrial fibrillation in the EPIC Norfolk cohort.
Eur J Prev Cardiol
PUBLISHED: 07-26-2014
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Identification of individuals at risk for developing atrial fibrillation (AF) will help to target screening and preventive interventions. We aimed to validate the CHARGE-AF model (including variables age, race, height, weight, blood pressure, smoking, antihypertensive medication, diabetes, myocardial infarction and heart failure) for prediction of five-year incident AF in a representative European population with a wide age range.
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Zhaoming Wang, Bin Zhu, Mingfeng Zhang, Hemang Parikh, Jinping Jia, Charles C Chung, Joshua N Sampson, Jason W Hoskins, Amy Hutchinson, Laurie Burdette, Abdisamad Ibrahim, Christopher Hautman, Preethi S Raj, Christian C Abnet, Andrew A Adjei, Anders Ahlbom, Demetrius Albanes, Naomi E Allen, Christine B Ambrosone, Melinda Aldrich, Pilar Amiano, Christopher Amos, Ulrika Andersson, Gerald Andriole, Irene L Andrulis, Cecilia Arici, Alan A Arslan, Melissa A Austin, Dalsu Baris, Donald A Barkauskas, Bryan A Bassig, Laura E Beane Freeman, Christine D Berg, Sonja I Berndt, Pier Alberto Bertazzi, Richard B Biritwum, Amanda Black, William Blot, Heiner Boeing, Paolo Boffetta, Kelly Bolton, Marie-Christine Boutron-Ruault, Paige M Bracci, Paul Brennan, Louise A Brinton, Michelle Brotzman, H Bas Bueno-de-Mesquita, Julie E Buring, Mary Ann Butler, Qiuyin Cai, Géraldine Cancel-Tassin, Federico Canzian, Guangwen Cao, Neil E Caporaso, Alfredo Carrato, Tania Carreon, Angela Carta, Gee-Chen Chang, I-Shou Chang, Jenny Chang-Claude, Xu Che, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chen, Anand P Chokkalingam, Lisa W Chu, Francoise Clavel-Chapelon, Graham A Colditz, Joanne S Colt, David Conti, Michael B Cook, Victoria K Cortessis, E David Crawford, Olivier Cussenot, Faith G Davis, Immaculata De Vivo, Xiang Deng, Ti Ding, Colin P Dinney, Anna Luisa Di Stefano, W Ryan Diver, Eric J Duell, Joanne W Elena, Jin-Hu Fan, Heather Spencer Feigelson, Maria Feychting, Jonine D Figueroa, Adrienne M Flanagan, Joseph F Fraumeni, Neal D Freedman, Brooke L Fridley, Charles S Fuchs, Manuela Gago-Dominguez, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Reina Garcia-Closas, Julie M Gastier-Foster, J Michael Gaziano, Daniela S Gerhard, Carol A Giffen, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Michael Goggins, Nalan Gokgoz, Alisa M Goldstein, Carlos González, Richard Gorlick, Mark H Greene, Myron Gross, H Barton Grossman, Robert Grubb, Jian Gu, Peng Guan, Christopher A Haiman, Göran Hallmans, Susan E Hankinson, Curtis C Harris, Patricia Hartge, Claudia Hattinger, Richard B Hayes, Qincheng He, Lee Helman, Brian E Henderson, Roger Henriksson, Judith Hoffman-Bolton, Chancellor Hohensee, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, H Dean Hosgood, Chin-Fu Hsiao, Ann W Hsing, Chao Agnes Hsiung, Nan Hu, Wei Hu, Zhibin Hu, Ming-Shyan Huang, David J Hunter, Peter D Inskip, Hidemi Ito, Eric J Jacobs, Kevin B Jacobs, Mazda Jenab, Bu-Tian Ji, Christoffer Johansen, Mattias Johansson, Alison Johnson, Rudolf Kaaks, Ashish M Kamat, Aruna Kamineni, Margaret Karagas, Chand Khanna, Kay-Tee Khaw, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kim, Chang Hyun Kang, Yoo Jin Jung, Cari M Kitahara, Alison P Klein, Robert Klein, Manolis Kogevinas, Woon-Puay Koh, Takashi Kohno, Laurence N Kolonel, Charles Kooperberg, Christian P Kratz, Vittorio Krogh, Hideo Kunitoh, Robert C Kurtz, Nilgun Kurucu, Qing Lan, Mark Lathrop, Ching C Lau, Fernando Lecanda, Kyoung-Mu Lee, Maxwell P Lee, Loic Le Marchand, Seth P Lerner, Donghui Li, Linda M Liao, Wei-Yen Lim, Dongxin Lin, Jie Lin, Sara Lindstrom, Martha S Linet, Jolanta Lissowska, Jianjun Liu, Börje Ljungberg, Josep Lloreta, Daru Lu, Jing Ma, Nuria Malats, Satu Mannisto, Neyssa Marina, Giuseppe Mastrangelo, Keitaro Matsuo, Katherine A McGlynn, Roberta Mckean-Cowdin, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Paul S Meltzer, James E Mensah, Xiaoping Miao, Dominique S Michaud, Alison M Mondul, Lee E Moore, Kenneth Muir, Shelley Niwa, Sara H Olson, Nick Orr, Salvatore Panico, Jae Yong Park, Alpa V Patel, Ana Patiño-García, Sofia Pavanello, Petra H M Peeters, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Piero Picci, Malcolm C Pike, Stefano Porru, Jennifer Prescott, Xia Pu, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Elio Riboli, Harvey A Risch, Rebecca J Rodabough, Nathaniel Rothman, Avima M Ruder, Jeong-Seon Ryu, Marc Sanson, Alan Schned, Fredrick R Schumacher, Ann G Schwartz, Kendra L Schwartz, Molly Schwenn, Katia Scotlandi, Adeline Seow, Consol Serra, Massimo Serra, Howard D Sesso, Gianluca Severi, Hongbing Shen, Min Shen, Sanjay Shete, Kouya Shiraishi, Xiao-Ou Shu, Afshan Siddiq, Luis Sierrasesúmaga, Sabina Sierri, Alan Dart Loon Sihoe, Debra T Silverman, Matthias Simon, Melissa C Southey, Logan Spector, Margaret Spitz, Meir Stampfer, Pär Stattin, Mariana C Stern, Victoria L Stevens, Rachael Z Stolzenberg-Solomon, Daniel O Stram, Sara S Strom, Wu-Chou Su, Malin Sund, Sook Whan Sung, Anthony Swerdlow, Wen Tan, Hideo Tanaka, Wei Tang, Ze-Zhang Tang, Adonina Tardón, Evelyn Tay, Philip R Taylor, Yao Tettey, David M Thomas, Roberto Tirabosco, Anne Tjonneland, Geoffrey S Tobias, Jorge R Toro, Ruth C Travis, Dimitrios Trichopoulos, Rebecca Troisi, Ann Truelove, Ying-Huang Tsai, Margaret A Tucker, Rosario Tumino, David Van Den Berg, Stephen K Van Den Eeden, Roel Vermeulen, Paolo Vineis, Kala Visvanathan, Ulla Vogel, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S Wang, Elisabete Weiderpass, Stephanie J Weinstein, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Alicja Wolk, Brian M Wolpin, Maria Pik Wong, Margaret Wrensch, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Yong-Bing Xiang, Jun Xu, Hannah P Yang, Pan-Chyr Yang, Yasushi Yatabe, Yuanqing Ye, Edward D Yeboah, Zhihua Yin, Chen Ying, Chong-Jen Yu, Kai Yu, Jian-Min Yuan, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Lisa Mirabello, Sharon A Savage, Peter Kraft, Stephen J Chanock, Meredith Yeager, Maria Terese Landi, Jianxin Shi, Nilanjan Chatterjee, Laufey T Amundadottir.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Michael V Holmes, Caroline E Dale, Luisa Zuccolo, Richard J Silverwood, Yiran Guo, Zheng Ye, David Prieto-Merino, Abbas Dehghan, Stella Trompet, Andrew Wong, Alana Cavadino, Dagmar Drogan, Sandosh Padmanabhan, Shanshan Li, Ajay Yesupriya, Maarten Leusink, Johan Sundström, Jaroslav A Hubacek, Hynek Pikhart, Daniel I Swerdlow, Andrie G Panayiotou, Svetlana A Borinskaya, Chris Finan, Sonia Shah, Karoline B Kuchenbaecker, Tina Shah, Jorgen Engmann, Lasse Folkersen, Per Eriksson, Fulvio Ricceri, Olle Melander, Carlotta Sacerdote, Dale M Gamble, Sruti Rayaprolu, Owen A Ross, Stela McLachlan, Olga Vikhireva, Ivonne Sluijs, Robert A Scott, Vera Adamkova, Leon Flicker, Frank M van Bockxmeer, Christine Power, Pedro Marques-Vidal, Tom Meade, Michael G Marmot, José M Ferro, Sofia Paulos-Pinheiro, Steve E Humphries, Philippa J Talmud, Irene Mateo Leach, Niek Verweij, Allan Linneberg, Tea Skaaby, Pieter A Doevendans, Maarten J Cramer, Pim van der Harst, Olaf H Klungel, Nicole F Dowling, Anna F Dominiczak, Meena Kumari, Andrew N Nicolaides, Cornelia Weikert, Heiner Boeing, Shah Ebrahim, Tom R Gaunt, Jackie F Price, Lars Lannfelt, Anne Peasey, Růžena Kubinova, Andrzej Pająk, Sofia Malyutina, Mikhail I Voevoda, Abdonas Tamosiunas, Anke H Maitland-van der Zee, Paul E Norman, Graeme J Hankey, Manuela M Bergmann, Albert Hofman, Oscar H Franco, Jackie Cooper, Jutta Palmen, Wilko Spiering, Pim A de Jong, Diana Kuh, Rebecca Hardy, André G Uitterlinden, M Arfan Ikram, Ian Ford, Elina Hyppönen, Osvaldo P Almeida, Nicholas J Wareham, Kay-Tee Khaw, Anders Hamsten, Lise Lotte N Husemoen, Anne Tjønneland, Janne S Tolstrup, Eric Rimm, Joline W J Beulens, W M Monique Verschuren, N Charlotte Onland-Moret, Marten H Hofker, S Goya Wannamethee, Peter H Whincup, Richard Morris, Astrid M Vicente, Hugh Watkins, Martin Farrall, J Wouter Jukema, James Meschia, L Adrienne Cupples, Stephen J Sharp, Myriam Fornage, Charles Kooperberg, Andrea Z LaCroix, James Y Dai, Matthew B Lanktree, David S Siscovick, Eric Jorgenson, Bonnie Spring, Josef Coresh, Yun R Li, Sarah G Buxbaum, Pamela J Schreiner, R Curtis Ellison, Michael Y Tsai, Sanjay R Patel, Susan Redline, Andrew D Johnson, Ron C Hoogeveen, Hakon Hakonarson, Jerome I Rotter, Eric Boerwinkle, Paul I W de Bakker, Mika Kivimäki, Folkert W Asselbergs, Naveed Sattar, Debbie A Lawlor, John Whittaker, George Davey Smith, Kenneth Mukamal, Bruce M Psaty, James G Wilson, Leslie A Lange, Ajna Hamidovic, Aroon D Hingorani, Børge G Nordestgaard, Martin Bobak, David A Leon, Claudia Langenberg, Tom M Palmer, Alex P Reiner, Brendan J Keating, Frank Dudbridge, Juan P Casas, .
BMJ
PUBLISHED: 07-12-2014
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To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.
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Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study.
Am. J. Clin. Nutr.
PUBLISHED: 07-02-2014
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Stable-isotope ratios of carbon ((13)C/(12)C, expressed as ?(13)C) and nitrogen ((15)N/(14)N, or ?(15)N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods.OBJECTIVE: The objective was to investigate dietary correlates of ?(13)C and ?(15)N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study.DESIGN: Serum ?(13)C and ?(15)N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of ?(13)C and ?(15)N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression.RESULTS: Mean (±SD) ?(13)C and ?(15)N were -22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and ?(13)C (r = 0.22) and ?(15)N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with ?(13)C but was significantly correlated with ?(15)N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ? 0.013). ?(13)C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas ?(15)N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001).CONCLUSIONS: The isotope ratios ?(13)C and ?(15)N may both serve as potential biomarkers of fish protein intake, whereas only ?(15)N may reflect broader animal-source protein intake in a European population. The inverse association of ?(13)C but a positive association of ?(15)N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.
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Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.
BMC Med
PUBLISHED: 06-27-2014
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Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
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Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease.
Heart
PUBLISHED: 06-27-2014
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To study the utility of body fat percentage in predicting health outcomes when other obesity indices are considered.
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Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: Results from the EPIC cohort study.
Int. J. Cancer
PUBLISHED: 06-17-2014
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Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.
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Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
Blood
PUBLISHED: 06-04-2014
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It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype-specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed significant increased risks of CLL (n = 102) with increasing mtDNA copy number (odds ratio = 1.34, 1.44, and 1.80 for quartiles 2-4, respectively; P trend = .001). mtDNA copy number was not associated with follow-up time, suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis.
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Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
John R B Perry, Felix Day, Cathy E Elks, Patrick Sulem, Deborah J Thompson, Teresa Ferreira, Chunyan He, Daniel I Chasman, Tonu Esko, Gudmar Thorleifsson, Eva Albrecht, Wei Q Ang, Tanguy Corre, Diana L Cousminer, Bjarke Feenstra, Nora Franceschini, Andrea Ganna, Andrew D Johnson, Sanela Kjellqvist, Kathryn L Lunetta, George McMahon, Ilja M Nolte, Lavinia Paternoster, Eleonora Porcu, Albert V Smith, Lisette Stolk, Alexander Teumer, Natalia Tšernikova, Emmi Tikkanen, Sheila Ulivi, Erin K Wagner, Najaf Amin, Laura J Bierut, Enda M Byrne, Jouke-Jan Hottenga, Daniel L Koller, Massimo Mangino, Tune H Pers, Laura M Yerges-Armstrong, Jing Hua Zhao, Irene L Andrulis, Hoda Anton-Culver, Femke Atsma, Stefania Bandinelli, Matthias W Beckmann, Javier Benitez, Carl Blomqvist, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Hiltrud Brauch, Hermann Brenner, Julie E Buring, Jenny Chang-Claude, Stephen Chanock, Jinhui Chen, Georgia Chenevix-Trench, J Margriet Collée, Fergus J Couch, David Couper, Andrea D Coviello, Angela Cox, Kamila Czene, Adamo Pio D'adamo, George Davey Smith, Immaculata De Vivo, Ellen W Demerath, Joe Dennis, Peter Devilee, Aida K Dieffenbach, Alison M Dunning, Gudny Eiriksdottir, Johan G Eriksson, Peter A Fasching, Luigi Ferrucci, Dieter Flesch-Janys, Henrik Flyger, Tatiana Foroud, Lude Franke, Melissa E Garcia, Montserrat Garcia-Closas, Frank Geller, Eco E J de Geus, Graham G Giles, Daniel F Gudbjartsson, Vilmundur Gudnason, Pascal Guénel, Suiqun Guo, Per Hall, Ute Hamann, Robin Haring, Catharina A Hartman, Andrew C Heath, Albert Hofman, Maartje J Hooning, John L Hopper, Frank B Hu, David J Hunter, David Karasik, Douglas P Kiel, Julia A Knight, Veli-Matti Kosma, Zoltan Kutalik, Sandra Lai, Diether Lambrechts, Annika Lindblom, Reedik Mägi, Patrik K Magnusson, Arto Mannermaa, Nicholas G Martin, Gisli Masson, Patrick F McArdle, Wendy L McArdle, Mads Melbye, Kyriaki Michailidou, Evelin Mihailov, Lili Milani, Roger L Milne, Heli Nevanlinna, Patrick Neven, Ellen A Nohr, Albertine J Oldehinkel, Ben A Oostra, Aarno Palotie, Munro Peacock, Nancy L Pedersen, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Dirkje S Postma, Anneli Pouta, Katri Pylkäs, Paolo Radice, Susan Ring, Fernando Rivadeneira, Antonietta Robino, Lynda M Rose, Anja Rudolph, Veikko Salomaa, Serena Sanna, David Schlessinger, Marjanka K Schmidt, Mellissa C Southey, Ulla Sovio, Meir J Stampfer, Doris Stöckl, Anna M Storniolo, Nicholas J Timpson, Jonathan Tyrer, Jenny A Visser, Peter Vollenweider, Henry Völzke, Gérard Waeber, Melanie Waldenberger, Henri Wallaschofski, Qin Wang, Gonneke Willemsen, Robert Winqvist, Bruce H R Wolffenbuttel, Margaret J Wright, , Dorret I Boomsma, Michael J Econs, Kay-Tee Khaw, Ruth J F Loos, Mark I McCarthy, Grant W Montgomery, John P Rice, Elizabeth A Streeten, Unnur Thorsteinsdottir, Cornelia M van Duijn, Behrooz Z Alizadeh, Sven Bergmann, Eric Boerwinkle, Heather A Boyd, Laura Crisponi, Paolo Gasparini, Christian Gieger, Tamara B Harris, Erik Ingelsson, Marjo-Riitta Järvelin, Peter Kraft, Debbie Lawlor, Andres Metspalu, Craig E Pennell, Paul M Ridker, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, David P Strachan, André G Uitterlinden, Nicholas J Wareham, Elisabeth Widén, Marek Zygmunt, Anna Murray, Douglas F Easton, Kari Stefansson, Joanne M Murabito, Ken K Ong.
Nature
PUBLISHED: 05-30-2014
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Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P?
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Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.
Int. J. Cancer
PUBLISHED: 05-16-2014
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ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio?=?1.84, 95%CI?=?1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.
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Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study.
Int. J. Cancer
PUBLISHED: 05-09-2014
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Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend?
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Post-GWAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.
Hum. Mol. Genet.
PUBLISHED: 05-08-2014
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We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 × 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
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Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
Nat. Genet.
PUBLISHED: 05-08-2014
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We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data.
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The association between Mediterranean Diet Score and glucokinase regulatory protein gene variation on the markers of cardiometabolic risk: an analysis in the European Prospective Investigation into Cancer (EPIC)-Norfolk study.
Br. J. Nutr.
PUBLISHED: 05-07-2014
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Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0-18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1%, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene-diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.
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Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition.
Int. J. Cancer
PUBLISHED: 04-17-2014
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Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR?=?1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR?=?1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction?=?0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear.
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Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
Int. J. Cancer
PUBLISHED: 03-27-2014
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High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Ali Amin Al Olama, Zsofia Kote-Jarai, Sonja I Berndt, David V Conti, Fredrick Schumacher, Ying Han, Sara Benlloch, Dennis J Hazelett, Zhaoming Wang, Ed Saunders, Daniel Leongamornlert, Sara Lindstrom, Sara Jugurnauth-Little, Tokhir Dadaev, Malgorzata Tymrakiewicz, Daniel O Stram, Kristin Rand, Peggy Wan, Alex Stram, Xin Sheng, Loreall C Pooler, Karen Park, Lucy Xia, Jonathan Tyrer, Laurence N Kolonel, Loic Le Marchand, Robert N Hoover, Mitchell J Machiela, Merideth Yeager, Laurie Burdette, Charles C Chung, Amy Hutchinson, Kai Yu, Chee Goh, Mahbubl Ahmed, Koveela Govindasami, Michelle Guy, Teuvo L J Tammela, Anssi Auvinen, Tiina Wahlfors, Johanna Schleutker, Tapio Visakorpi, Katri A Leinonen, Jianfeng Xu, Markus Aly, Jenny Donovan, Ruth C Travis, Tim J Key, Afshan Siddiq, Federico Canzian, Kay-Tee Khaw, Atsushi Takahashi, Michiaki Kubo, Paul Pharoah, Nora Pashayan, Maren Weischer, Borge G Nordestgaard, Sune F Nielsen, Peter Klarskov, Martin Andreas Røder, Peter Iversen, Stephen N Thibodeau, Shannon K McDonnell, Daniel J Schaid, Janet L Stanford, Suzanne Kolb, Sarah Holt, Beatrice Knudsen, Antonio Hurtado Coll, Susan M Gapstur, W Ryan Diver, Victoria L Stevens, Christiane Maier, Manuel Luedeke, Kathleen Herkommer, Antje E Rinckleb, Sara S Strom, Curtis Pettaway, Edward D Yeboah, Yao Tettey, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Anand P Chokkalingam, Lisa Cannon-Albright, Cezary Cybulski, Dominika Wokołorczyk, Wojciech Kluźniak, Jong Park, Thomas Sellers, Hui-Yi Lin, William B Isaacs, Alan W Partin, Hermann Brenner, Aida Karina Dieffenbach, Christa Stegmaier, Constance Chen, Edward L Giovannucci, Jing Ma, Meir Stampfer, Kathryn L Penney, Lorelei Mucci, Esther M John, Sue A Ingles, Rick A Kittles, Adam B Murphy, Hardev Pandha, Agnieszka Michael, Andrzej M Kierzek, William Blot, Lisa B Signorello, Wei Zheng, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Barbara Nemesure, John Carpten, Cristina Leske, Suh-Yuh Wu, Anselm Hennis, Adam S Kibel, Benjamin A Rybicki, Christine Neslund-Dudas, Ann W Hsing, Lisa Chu, Phyllis J Goodman, Eric A Klein, S Lilly Zheng, Jyotsna Batra, Judith Clements, Amanda Spurdle, Manuel R Teixeira, Paula Paulo, Sofia Maia, Chavdar Slavov, Radka Kaneva, Vanio Mitev, John S Witte, Graham Casey, Elizabeth M Gillanders, Daniella Seminara, Elio Riboli, Freddie C Hamdy, Gerhard A Coetzee, Qiyuan Li, Matthew L Freedman, David J Hunter, Kenneth Muir, Henrik Grönberg, David E Neal, Melissa Southey, Graham G Giles, Gianluca Severi, , Michael B Cook, Hidewaki Nakagawa, Fredrik Wiklund, Peter Kraft, Stephen J Chanock, Brian E Henderson, Douglas F Easton, Rosalind A Eeles, Christopher A Haiman.
Nat. Genet.
PUBLISHED: 03-26-2014
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Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
Brian M Wolpin, Cosmeri Rizzato, Peter Kraft, Charles Kooperberg, Gloria M Petersen, Zhaoming Wang, Alan A Arslan, Laura Beane-Freeman, Paige M Bracci, Julie Buring, Federico Canzian, Eric J Duell, Steven Gallinger, Graham G Giles, Gary E Goodman, Phyllis J Goodman, Eric J Jacobs, Aruna Kamineni, Alison P Klein, Laurence N Kolonel, Matthew H Kulke, Donghui Li, Nuria Malats, Sara H Olson, Harvey A Risch, Howard D Sesso, Kala Visvanathan, Emily White, Wei Zheng, Christian C Abnet, Demetrius Albanes, Gabriella Andreotti, Melissa A Austin, Richard Barfield, Daniela Basso, Sonja I Berndt, Marie-Christine Boutron-Ruault, Michelle Brotzman, Markus W Büchler, H Bas Bueno-de-Mesquita, Peter Bugert, Laurie Burdette, Daniele Campa, Neil E Caporaso, Gabriele Capurso, Charles Chung, Michelle Cotterchio, Eithne Costello, Joanne Elena, Niccola Funel, J Michael Gaziano, Nathalia A Giese, Edward L Giovannucci, Michael Goggins, Megan J Gorman, Myron Gross, Christopher A Haiman, Manal Hassan, Kathy J Helzlsouer, Brian E Henderson, Elizabeth A Holly, Nan Hu, David J Hunter, Federico Innocenti, Mazda Jenab, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Eric A Klein, Manolis Kogevinas, Vittorio Krogh, Juozas Kupcinskas, Robert C Kurtz, Andrea LaCroix, Maria T Landi, Stefano Landi, Loic Le Marchand, Andrea Mambrini, Satu Mannisto, Roger L Milne, Yusuke Nakamura, Ann L Oberg, Kouros Owzar, Alpa V Patel, Petra H M Peeters, Ulrike Peters, Raffaele Pezzilli, Ada Piepoli, Miquel Porta, Francisco X Real, Elio Riboli, Nathaniel Rothman, Aldo Scarpa, Xiao-Ou Shu, Debra T Silverman, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Philip R Taylor, George E Theodoropoulos, Mark Thornquist, Anne Tjønneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Pavel Vodicka, Jean Wactawski-Wende, Nicolas Wentzensen, Chen Wu, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Robert Hoover, Patricia Hartge, Charles Fuchs, Stephen J Chanock, Rachael S Stolzenberg-Solomon, Laufey T Amundadottir.
Nat. Genet.
PUBLISHED: 02-26-2014
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We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
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Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.
Jeannette Simino, Gang Shi, Joshua C Bis, Daniel I Chasman, Georg B Ehret, Xiangjun Gu, Xiuqing Guo, Shih-Jen Hwang, Eric Sijbrands, Albert V Smith, Germaine C Verwoert, Jennifer L Bragg-Gresham, Gemma Cadby, Peng Chen, Ching-Yu Cheng, Tanguy Corre, Rudolf A de Boer, Anuj Goel, Toby Johnson, Chiea-Chuen Khor, , Carla Lluis-Ganella, Jian'an Luan, Leo-Pekka Lyytikäinen, Ilja M Nolte, Xueling Sim, Siim Sõber, Peter J van der Most, Niek Verweij, Jing Hua Zhao, Najaf Amin, Eric Boerwinkle, Claude Bouchard, Abbas Dehghan, Gudny Eiriksdottir, Roberto Elosua, Oscar H Franco, Christian Gieger, Tamara B Harris, Serge Hercberg, Albert Hofman, Alan L James, Andrew D Johnson, Mika Kähönen, Kay-Tee Khaw, Zoltan Kutalik, Martin G Larson, Lenore J Launer, Guo Li, Jianjun Liu, Kiang Liu, Alanna C Morrison, Gerjan Navis, Rick Twee-Hee Ong, George J Papanicolau, Brenda W Penninx, Bruce M Psaty, Leslie J Raffel, Olli T Raitakari, Kenneth Rice, Fernando Rivadeneira, Lynda M Rose, Serena Sanna, Robert A Scott, David S Siscovick, Ronald P Stolk, André G Uitterlinden, Dhananjay Vaidya, Melanie M van der Klauw, Ramachandran S Vasan, Eranga Nishanthie Vithana, Uwe Völker, Henry Völzke, Hugh Watkins, Terri L Young, Tin Aung, Murielle Bochud, Martin Farrall, Catharina A Hartman, Maris Laan, Edward G Lakatta, Terho Lehtimäki, Ruth J F Loos, Gavin Lucas, Pierre Meneton, Lyle J Palmer, Rainer Rettig, Harold Snieder, E Shyong Tai, Yik-Ying Teo, Pim van der Harst, Nicholas J Wareham, Cisca Wijmenga, Tien Yin Wong, Myriam Fornage, Vilmundur Gudnason, Daniel Levy, Walter Palmas, Paul M Ridker, Jerome I Rotter, Cornelia M van Duijn, Jacqueline C M Witteman, Aravinda Chakravarti, Dabeeru C Rao.
Am. J. Hum. Genet.
PUBLISHED: 02-22-2014
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Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ? 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.
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Low bone mineral density predicts incident heart failure in men and women: the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk prospective study.
JACC Heart Fail
PUBLISHED: 02-20-2014
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It is unknown whether bone mineral density as a measure of osteoporosis is associated with development of heart failure.
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Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations.
J. Nutr.
PUBLISHED: 12-24-2013
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Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.
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Visual acuity, self-reported vision and falls in the EPIC-Norfolk Eye study.
Br J Ophthalmol
PUBLISHED: 12-12-2013
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To examine the relationship between visual acuity (VA) and self-reported vision (SRV) in relation to falls in 8317 participants of the European Prospective Investigation into Cancer-Norfolk Eye study.
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The association of cycling with all-cause, cardiovascular and cancer mortality: findings from the population-based EPIC-Norfolk cohort.
BMJ Open
PUBLISHED: 11-16-2013
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To investigate associations between modest levels of total and domain-specific (commuting, other utility, recreational) cycling and mortality from all causes, cardiovascular disease and cancer.
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Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-Results from the EPIC cohort study.
Int. J. Cancer
PUBLISHED: 11-06-2013
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Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7?±?8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.
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Genes-Environment Interactions in Obesity- and Diabetes-Associated Pancreatic Cancer: A GWAS Data Analysis.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-17-2013
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Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level.
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The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations: The EPIC-InterAct study.
Diabetes Care
PUBLISHED: 10-15-2013
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OBJECTIVE To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis. RESULTS In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes. CONCLUSIONS Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
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N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-03-2013
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An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition.
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The Association Between Circulating Lipoprotein(a) and Type 2 Diabetes: Is It Causal?
Diabetes
PUBLISHED: 10-02-2013
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Epidemiological evidence supports a direct and causal association between lipoprotein(a) [Lp(a)] levels and coronary risk, but the nature of the association between Lp(a) levels and risk of type 2 diabetes (T2D) is unclear. In this study, we assessed the association of Lp(a) levels with risk of incident T2D and tested whether Lp(a) levels are causally linked to T2D. We analyzed data on 18,490 participants from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort that included adults aged 40-79 years at baseline 1993-1997. During an average 10 years of follow-up, 593 participants developed incident T2D. Cox regression models were used to estimate the association between Lp(a) levels and T2D. In Mendelian randomization analyses, based on EPIC-Norfolk combined with DIAbetes Genetics Replication And Meta-analysis data involving a total of 10,088 diabetes case participants and 68,346 control participants, we used a genetic variant (rs10455872) as an instrument to test whether the association between Lp(a) levels and T2D is causal. In adjusted analyses, there was an inverse association between Lp(a) levels and T2D: hazard ratio was 0.63 (95% CI 0.49-0.81; P trend = 0.003) comparing the top versus bottom quintile of Lp(a). In EPIC-Norfolk, a 1-SD increase in logLp(a) was associated with a lower risk of T2D (odds ratio [OR] 0.88 [95% CI: 0.80-0.95]). However, in Mendelian randomization analyses, a 1-SD increase in logLp(a) due to rs10455872, which explained 26.8% of the variability in Lp(a) levels, was not associated with risk of T2D (OR 1.03 [0.96-1.10]; P = 0.41). These prospective findings demonstrate a strong inverse association of Lp(a) levels with risk of T2D. However, a genetic variant that elevated Lp(a) levels was not associated with risk of T2D, suggesting that elevated Lp(a) levels are not causally associated with a lower risk of T2D.
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C-reactive protein, fatal and nonfatal coronary artery disease, stroke, and peripheral artery disease in the prospective EPIC-Norfolk cohort study.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 09-26-2013
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Circulating levels of C-reactive protein (CRP) are associated with an increased risk of coronary artery disease (CAD), stroke, and peripheral artery disease (PAD). Observational and experimental evidence suggest that CRP might differentially predict fatal and nonfatal cardiovascular events. Here, we sought to determine the predictive value of CRP for fatal and nonfatal CAD, stroke, or PAD.
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Longitudinal Association of C-Reactive Protein and Lung Function Over 13 Years: The EPIC-Norfolk Study.
Am. J. Epidemiol.
PUBLISHED: 09-24-2013
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Chronic obstructive pulmonary disease is known to be associated with systemic inflammation. We examined the longitudinal association of C-reactive protein (CRP) and lung function in a cohort of 18,110 men and women from the European Prospective Investigation Into Cancer in Norfolk who were 40-79 years of age at baseline (recruited in 1993-1997) and followed-up through 2011. We assessed lung function by measuring forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at baseline, 4 years, and 13 years. Serum CRP levels were measured using a high-sensitivity assay at baseline and the 13-year follow up. Cross-sectional and longitudinal associations of loge-CRP and lung function were examined using multivariable linear mixed models. In the cross-sectional analysis, 1-standard-deviation increase in baseline loge-CRP (about 3-fold higher CRP on the original milligrams per liter scale) was associated with a -86.3 mL (95% confidence interval: -93.9, -78.6) reduction in FEV1. In longitudinal analysis, a 1-standard-deviation increase in loge-CRP over 13 years was also associated with a -64.0 mL (95% confidence interval: -72.1, -55.8) decline in FEV1 over the same period. The associations were similar for FVC and persisted among lifetime never-smokers. Baseline CRP levels were not predictive of the rate of change in FEV1 or FVC over time. In the present study, we found longitudinal observational evidence that suggested that increases in systemic inflammation are associated with declines in lung function.
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Dietary intake measurement using 7 d diet diaries in British men and women in the European Prospective Investigation into Cancer-Norfolk study: a focus on methodological issues.
Br. J. Nutr.
PUBLISHED: 09-17-2013
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The aim of the present study was to describe the energy, nutrient and crude v. disaggregated food intake measured using 7 d diet diaries (7dDD) for the full baseline Norfolk cohort recruited for the European Prospective Investigation into Cancer (EPIC-Norfolk) study, with emphasis on methodological issues. The first data collection took place between 1993 and 1998 in Norfolk, East Anglia (UK). Of the 30 445 men and women, aged 40-79 years, registered with a general practitioner invited to participate in the study, 25 639 came for a health examination and were asked to complete a 7dDD. Data from diaries with data recorded for at least 1 d were obtained for 99 % members of the cohort; 10 354 (89·8 %) of the men and 12 779 (91·5 %) of the women completed the diet diaries for all 7 d. Mean energy intake (EI) was 9·44 (sd 2·22) MJ/d and 7·15 (sd 1·66) MJ/d, respectively. EI remained approximately stable across the days, but there was apparent under-reporting among the participants, especially among those with BMI >25 kg/m2. Micronutrient density was higher among women than among men. In conclusion, under-reporting is an issue, but not more so than that found in national surveys. How foods were grouped (crude or disaggregated) made a difference to the estimates obtained, and comparison of intakes showed wide limits of agreement. The choice of variables influences estimates obtained from the food group data; while this may not alter the ranking of individuals within studies, this issue may be relevant when comparing absolute food intakes between studies.
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Laser scanning tomography in the EPIC-Norfolk Eye Study: principal components and associations.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 09-14-2013
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To describe Heidelberg Retina Tomograph (HRT) measures, their principal components, and their associations in a British population.
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Discovery and refinement of loci associated with lipid levels.
, Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M den Hertog, Ron Do, Louise A Donnelly, Georg B Ehret, Tonu Esko, Mary F Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Martina Müller-Nurasyid, Ilja M Nolte, Jeffrey R O'Connell, Cameron D Palmer, Markus Perola, Ann-Kristin Petersen, Serena Sanna, Richa Saxena, Susan K Service, Sonia Shah, Dmitry Shungin, Carlo Sidore, Ci Song, Rona J Strawbridge, Ida Surakka, Toshiko Tanaka, Tanya M Teslovich, Gudmar Thorleifsson, Evita G van den Herik, Benjamin F Voight, Kelly A Volcik, Lindsay L Waite, Andrew Wong, Ying Wu, Weihua Zhang, Devin Absher, Gershim Asiki, Inês Barroso, Latonya F Been, Jennifer L Bolton, Lori L Bonnycastle, Paolo Brambilla, Mary S Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S F Doney, Angela Döring, Paul Elliott, Stephen E Epstein, Gudmundur Ingi Eyjolfsson, Bruna Gigante, Mark O Goodarzi, Harald Grallert, Martha L Gravito, Christopher J Groves, Göran Hallmans, Anna-Liisa Hartikainen, Caroline Hayward, Dena Hernandez, Andrew A Hicks, Hilma Holm, Yi-Jen Hung, Thomas Illig, Michelle R Jones, Pontiano Kaleebu, John J P Kastelein, Kay-Tee Khaw, Eric Kim, Norman Klopp, Pirjo Komulainen, Meena Kumari, Claudia Langenberg, Terho Lehtimäki, Shih-Yi Lin, Jaana Lindström, Ruth J F Loos, François Mach, Wendy L McArdle, Christa Meisinger, Braxton D Mitchell, Gabrielle Müller, Ramaiah Nagaraja, Narisu Narisu, Tuomo V M Nieminen, Rebecca N Nsubuga, Isleifur Olafsson, Ken K Ong, Aarno Palotie, Theodore Papamarkou, Cristina Pomilla, Anneli Pouta, Daniel J Rader, Muredach P Reilly, Paul M Ridker, Fernando Rivadeneira, Igor Rudan, Aimo Ruokonen, Nilesh Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stančáková, Kathleen Stirrups, Amy J Swift, Laurence Tiret, André G Uitterlinden, L Joost van Pelt, Sailaja Vedantam, Nicholas Wainwright, Cisca Wijmenga, Sarah H Wild, Gonneke Willemsen, Tom Wilsgaard, James F Wilson, Elizabeth H Young, Jing Hua Zhao, Linda S Adair, Dominique Arveiler, Themistocles L Assimes, Stefania Bandinelli, Franklyn Bennett, Murielle Bochud, Bernhard O Boehm, Dorret I Boomsma, Ingrid B Borecki, Stefan R Bornstein, Pascal Bovet, Michel Burnier, Harry Campbell, Aravinda Chakravarti, John C Chambers, Yii-Der Ida Chen, Francis S Collins, Richard S Cooper, John Danesh, George Dedoussis, Ulf de Faire, Alan B Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B Freimer, Christian Gieger, Leif C Groop, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Aroon Hingorani, Joel N Hirschhorn, Albert Hofman, G Kees Hovingh, Chao Agnes Hsiung, Steve E Humphries, Steven C Hunt, Kristian Hveem, Carlos Iribarren, Marjo-Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimäki, Jaspal S Kooner, Peter J Koudstaal, Ronald M Krauss, Diana Kuh, Johanna Kuusisto, Kirsten O Kyvik, Markku Laakso, Timo A Lakka, Lars Lind, Cecilia M Lindgren, Nicholas G Martin, Winfried März, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Andres Metspalu, Leena Moilanen, Andrew D Morris, Patricia B Munroe, Inger Njølstad, Nancy L Pedersen, Chris Power, Peter P Pramstaller, Jackie F Price, Bruce M Psaty, Thomas Quertermous, Rainer Rauramaa, Danish Saleheen, Veikko Salomaa, Dharambir K Sanghera, Jouko Saramies, Peter E H Schwarz, Wayne H-H Sheu, Alan R Shuldiner, Agneta Siegbahn, Tim D Spector, Kari Stefansson, David P Strachan, Bamidele O Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M van Duijn, Peter Vollenweider, Lars Wallentin, Nicholas J Wareham, John B Whitfield, Bruce H R Wolffenbuttel, José M Ordovás, Eric Boerwinkle, Colin N A Palmer, Unnur Thorsteinsdottir, Daniel I Chasman, Jerome I Rotter, Paul W Franks, Samuli Ripatti, L Adrienne Cupples, Manjinder S Sandhu, Stephen S Rich, Michael Boehnke, Panos Deloukas, Sekar Kathiresan, Karen L Mohlke, Erik Ingelsson, Gonçalo R Abecasis.
Nat. Genet.
PUBLISHED: 09-13-2013
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Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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The Systematic COronary Risk Evaluation (SCORE) in a large UK population: 10-year follow-up in the EPIC-Norfolk prospective population study.
Eur J Prev Cardiol
PUBLISHED: 09-05-2013
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The European Society of Cardiology endorses cardiovascular disease (CVD) risk stratification using the Systematic COronary Risk Evaluation (SCORE) algorithm, with separate algorithms for high-risk and low-risk countries. In the 2012 European Guidelines on CVD Prevention in Clinical Practice, the UK has been reclassified as a low-risk country. However, the performance of the SCORE algorithm has not been validated in the UK.
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Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort.
Int. J. Cancer
PUBLISHED: 07-12-2013
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Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 ?=?1.56 (95% CI 1.15-2.13), ptrend ?=?0.02 for testosterone and ORQ4-Q1 ?=?1.33 (95% CI 0.99-1.79), ptrend ?=?0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 ?=?1.32 (95% CI 0.87-2.01), ptrend ?=?0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 ?=?0.94 (95% CI 0.60-1.47), ptrend ?=?0.34, phet ?=?0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.
Int. J. Cancer
PUBLISHED: 06-18-2013
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Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 ?=?1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR?=?1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend ?=?0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 ?=?1.38 [95% CI 1.01-1.89]; OR?=?1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend ?=?0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet ?=?0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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The physical capability of community-based men and women from a British cohort: the European Prospective Investigation into Cancer (EPIC)-Norfolk study.
BMC Geriatr
PUBLISHED: 05-21-2013
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The European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (?0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study.
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Social relationships and healthful dietary behaviour: Evidence from over-50s in the EPIC cohort, UK.
Soc Sci Med
PUBLISHED: 04-10-2013
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Social relationships are an important aspect of a persons social environment that can protect against a wide range of chronic conditions and facilitate recovery from disease. Social relationships have also been linked to dietary behaviour which may be an important pathway through which social circumstances exert their influence on health. Yet, questions remain about which structural aspects of social relationships most affect healthful dietary behaviours and whether different structural components interact to produce a combined effect. Using data from adults (?50 years) in the European Prospective Investigation of Cancer-Norfolk study (1996-2002), we examined marital status, living arrangement and social isolation in relation to scores for variety of fruit and vegetable intake as a marker of diet quality associated with adverse health outcomes. Data were analysed with multivariable linear regression models for gender-specific and interaction associations. We found that being single or widowed was associated with a lower variety score, particularly vegetable variety, and associations were enhanced when combined with male gender, living alone or infrequent friend contact. Lower variety scores for lone-living were also observed, especially for men. Infrequent friend contact interacted with living arrangement to amplify negative associations of lone-living with variety, with statistically significant differences in contact frequency for vegetable variety. Lower levels of friend contact were associated with reduced variety of fruits and vegetables in a graded trend for both genders; the trend was more pronounced among men. Family contact appeared to have limited association with vegetable variety in men; among women, weekly contact was significantly and positively associated with vegetable variety compared to daily family contact. Results highlight the importance of considering living arrangement and/or frequency of social contact when assessing whether widowed, single or lone-living older adults are at risk of lower fruit and vegetable variety.
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Common variants associated with plasma triglycerides and risk for coronary artery disease.
Ron Do, Cristen J Willer, Ellen M Schmidt, Sebanti Sengupta, Chi Gao, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M den Hertog, Louise A Donnelly, Georg B Ehret, Tonu Esko, Mary F Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Martina Müller-Nurasyid, Ilja M Nolte, Jeffrey R O'Connell, Cameron D Palmer, Markus Perola, Ann-Kristin Petersen, Serena Sanna, Richa Saxena, Susan K Service, Sonia Shah, Dmitry Shungin, Carlo Sidore, Ci Song, Rona J Strawbridge, Ida Surakka, Toshiko Tanaka, Tanya M Teslovich, Gudmar Thorleifsson, Evita G van den Herik, Benjamin F Voight, Kelly A Volcik, Lindsay L Waite, Andrew Wong, Ying Wu, Weihua Zhang, Devin Absher, Gershim Asiki, Inês Barroso, Latonya F Been, Jennifer L Bolton, Lori L Bonnycastle, Paolo Brambilla, Mary S Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S F Doney, Angela Döring, Paul Elliott, Stephen E Epstein, Gudmundur Ingi Eyjolfsson, Bruna Gigante, Mark O Goodarzi, Harald Grallert, Martha L Gravito, Christopher J Groves, Göran Hallmans, Anna-Liisa Hartikainen, Caroline Hayward, Dena Hernandez, Andrew A Hicks, Hilma Holm, Yi-Jen Hung, Thomas Illig, Michelle R Jones, Pontiano Kaleebu, John J P Kastelein, Kay-Tee Khaw, Eric Kim, Norman Klopp, Pirjo Komulainen, Meena Kumari, Claudia Langenberg, Terho Lehtimäki, Shih-Yi Lin, Jaana Lindström, Ruth J F Loos, François Mach, Wendy L McArdle, Christa Meisinger, Braxton D Mitchell, Gabrielle Müller, Ramaiah Nagaraja, Narisu Narisu, Tuomo V M Nieminen, Rebecca N Nsubuga, Isleifur Olafsson, Ken K Ong, Aarno Palotie, Theodore Papamarkou, Cristina Pomilla, Anneli Pouta, Daniel J Rader, Muredach P Reilly, Paul M Ridker, Fernando Rivadeneira, Igor Rudan, Aimo Ruokonen, Nilesh Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stančáková, Kathleen Stirrups, Amy J Swift, Laurence Tiret, André G Uitterlinden, L Joost van Pelt, Sailaja Vedantam, Nicholas Wainwright, Cisca Wijmenga, Sarah H Wild, Gonneke Willemsen, Tom Wilsgaard, James F Wilson, Elizabeth H Young, Jing Hua Zhao, Linda S Adair, Dominique Arveiler, Themistocles L Assimes, Stefania Bandinelli, Franklyn Bennett, Murielle Bochud, Bernhard O Boehm, Dorret I Boomsma, Ingrid B Borecki, Stefan R Bornstein, Pascal Bovet, Michel Burnier, Harry Campbell, Aravinda Chakravarti, John C Chambers, Yii-Der Ida Chen, Francis S Collins, Richard S Cooper, John Danesh, George Dedoussis, Ulf de Faire, Alan B Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B Freimer, Christian Gieger, Leif C Groop, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Aroon Hingorani, Joel N Hirschhorn, Albert Hofman, G Kees Hovingh, Chao Agnes Hsiung, Steve E Humphries, Steven C Hunt, Kristian Hveem, Carlos Iribarren, Marjo-Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimäki, Jaspal S Kooner, Peter J Koudstaal, Ronald M Krauss, Diana Kuh, Johanna Kuusisto, Kirsten O Kyvik, Markku Laakso, Timo A Lakka, Lars Lind, Cecilia M Lindgren, Nicholas G Martin, Winfried März, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Andres Metspalu, Leena Moilanen, Andrew D Morris, Patricia B Munroe, Inger Njølstad, Nancy L Pedersen, Chris Power, Peter P Pramstaller, Jackie F Price, Bruce M Psaty, Thomas Quertermous, Rainer Rauramaa, Danish Saleheen, Veikko Salomaa, Dharambir K Sanghera, Jouko Saramies, Peter E H Schwarz, Wayne H-H Sheu, Alan R Shuldiner, Agneta Siegbahn, Tim D Spector, Kari Stefansson, David P Strachan, Bamidele O Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M van Duijn, Peter Vollenweider, Lars Wallentin, Nicholas J Wareham, John B Whitfield, Bruce H R Wolffenbuttel, David Altshuler, José M Ordovás, Eric Boerwinkle, Colin N A Palmer, Unnur Thorsteinsdottir, Daniel I Chasman, Jerome I Rotter, Paul W Franks, Samuli Ripatti, L Adrienne Cupples, Manjinder S Sandhu, Stephen S Rich, Michael Boehnke, Panos Deloukas, Karen L Mohlke, Erik Ingelsson, Gonçalo R Abecasis, Mark J Daly, Benjamin M Neale, Sekar Kathiresan.
Nat. Genet.
PUBLISHED: 02-20-2013
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Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphisms effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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Methylome analysis and epigenetic changes associated with menarcheal age.
PLoS ONE
PUBLISHED: 01-01-2013
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Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12-14vs.?11 yrs:1.78, 95%CI:1.01-3.17 and OR?15vs.?11 yrs:4.59, 95%CI:2.04-10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.
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Crowdsourcing as a novel technique for retinal fundus photography classification: analysis of images in the EPIC Norfolk cohort on behalf of the UK Biobank Eye and Vision Consortium.
PLoS ONE
PUBLISHED: 01-01-2013
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Crowdsourcing is the process of outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing for the classification of retinal fundus photography.
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Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Br. J. Nutr.
PUBLISHED: 12-20-2011
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Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35-74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.
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Differential white blood cell count and incident heart failure in men and women in the EPIC-Norfolk study.
Eur. Heart J.
PUBLISHED: 12-15-2011
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Markers of inflammation are associated with increased risk of heart failure, but data on differential white blood cell (WBC) count are lacking. We examined the prospective association between differential WBC count and incident heart failure events.
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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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