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Find video protocols related to scientific articles indexed in Pubmed.
Racial diversity of actionable mutations in non-small cell lung cancer.
J Thorac Oncol
PUBLISHED: 11-08-2014
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Lung cancer is the leading cause of cancer-related deaths in the United States. The reasons for higher incidence and poorer survival rates among black compared to white lung cancer patients have not been defined. We hypothesized that differential incidence of somatic cancer gene mutations may be a contributing factor. Previous genomic studies of non-small cell lung cancer (NSCLC) have not adequately represented black patients.
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Clinical characteristics of breast cancers in african-american women with benign breast disease: a comparison to the surveillance, epidemiology, and end results program.
Breast J
PUBLISHED: 09-08-2014
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Benign breast disease (BBD) is a very common condition, diagnosed in approximately half of all American women throughout their lifecourse. White women with BBD are known to be at substantially increased risk of subsequent breast cancer; however, nothing is known about breast cancer characteristics that develop after a BBD diagnosis in African-American women. Here, we compared 109 breast cancers that developed in a population of African-American women with a history of BBD to 10,601 breast cancers that developed in a general population of African-American women whose cancers were recorded by the Metropolitan Detroit Cancer Surveillance System (MDCSS population). Demographic and clinical characteristics of the BBD population were compared to the MDCSS population, using chi-squared tests, Fisher's exact tests, t-tests, and Wilcoxon tests where appropriate. Kaplan-Meier curves and Cox regression models were used to examine survival. Women in the BBD population were diagnosed with lower grade (p = 0.02), earlier stage cancers (p = 0.003) that were more likely to be hormone receptor-positive (p = 0.03) compared to the general metropolitan Detroit African-American population. In situ cancers were more common among women in the BBD cohort (36.7%) compared to the MDCSS population (22.1%, p < 0.001). Overall, women in the BBD population were less likely to die from breast cancer after 10 years of follow-up (p = 0.05), but this association was not seen when analyses were limited to invasive breast cancers. These results suggest that breast cancers occurring after a BBD diagnosis may have more favorable clinical parameters, but the majority of cancers are still invasive, with survival rates similar to the general African-American population.
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BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.
Genet. Med.
PUBLISHED: 08-05-2014
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Purpose:Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.Methods:Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.Results:Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.Conclusion:Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med advance online publication 06 November 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.153.
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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.
Carcinogenesis
PUBLISHED: 05-15-2014
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Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.
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Apoptosis-Related Single Nucleotide Polymorphisms and the Risk of Non-Small Cell Lung Cancer in Women.
J Cancer Ther Res
PUBLISHED: 05-03-2014
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Germline apoptosis-related single nucleotide polymorphisms (SNPs) have been shown to contribute to the risk of developing non-small cell lung cancer (NSCLC). However, very few studies have looked specifically at apoptosis-related SNPs in a racially-stratified analysis of white and African-American women.
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Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease.
Cancer Res.
PUBLISHED: 04-22-2014
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Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile = 1.80; 95% confidence interval, CI, 1.16-2.79; Ptrend = 0.003) as were levels of estradiol (OR for highest vs. lowest tertile = 1.89; 95% CI, 1.26-2.83; Ptrend = 0.02) and CRP (OR for highest vs. lowest quartile = 2.46; 95% CI, 1.59-3.80; Ptrend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile = 0.47; 95% CI, 0.31-0.71; Ptrend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development.
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The influence of comorbid conditions on racial disparities in endometrial cancer survival.
Am. J. Obstet. Gynecol.
PUBLISHED: 02-28-2014
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There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race.
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Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).
Int. J. Cancer
PUBLISHED: 01-30-2014
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While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.
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Oropharyngeal carcinoma in young adults: an alarming national trend.
Otolaryngol Head Neck Surg
PUBLISHED: 01-22-2014
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To assess the incidence, treatment methods, and outcomes of oropharyngeal squamous cell carcinoma (OPSCC) in patients younger than 45 years.
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Re-contacting participants for inclusion in the database of Genotypes and Phenotypes (dbGaP): Findings from three case-control studies of lung cancer.
Genome Med
PUBLISHED: 01-01-2014
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Since January 2008, the National Institutes of Health (NIH) has required that all investigators who receive NIH support submit de-identified high-throughput genomic data to the database of Genotypes and Phenotypes (dbGaP). The purpose of this study was to explore the feasibility of re-consenting participants from three inactive studies, conducted from 2000 through 2009, to submit their data to dbGaP.
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Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.
Anticancer Res.
PUBLISHED: 11-14-2013
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To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC).
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Treatment patterns for cervical carcinoma in situ in michigan, 1998-2003.
J Registry Manag
PUBLISHED: 09-05-2013
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Objective: To characterize population-level surgical treatment patterns for cervical carcinoma in situ (CIS) reported to the Michigan Cancer Surveillance Program (MCSP), and to inform data collection strategies. Methods: All cases of cervical carcinoma in situ (CIS) (including cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ [AIS]) reported to the MCSP during 1998-2003 were identified. First course of treatment (ablative procedure, cone biopsy, loop electrosurgical excisional procedure [LEEP], hysterectomy, unspecified surgical treatment, no surgical treatment, unknown if surgically treated) was described by histology, race, and age at diagnosis. Results: Of 17,022 cases of cervical CIS, 82.8 percent were squamous CIS, 3 percent AIS/adenosquamous CIS, and 14.2 percent unspecified/other CIS. Over half (54.7 percent) of cases were diagnosed in women under age 30. Excisional treatments (LEEP, 32.3 percent and cone biopsy, 17.3 percent) were most common, though substantial proportions had no reported treatment (17.8 percent) or unknown treatment (21.1 percent). Less common were hysterectomy (7.2 percent) and ablative procedures (2.6 percent). LEEP was the most common treatment for squamous cases, while hysterectomy was the most treatment for AIS/adenosquamous CIS cases. Across histologic types, a sizeable proportion of women diagnosed ?30 years of age underwent excision, either LEEP (20 percent-38.7 percent) or cone biopsy (13.7 percent-44 percent). Conclusion: Despite evidence suggesting it may be safer and equally effective as excision, ablation was rarely used for treating cervical squamous CIS. These population-based data indicate some notable differences in treatment by histology and age at diagnosis, with observed patterns appearing consistent with consensus guidelines in place at the time of study, but favoring more aggressive procedures. Future data collection strategies may need to validate treatment information, including the large proportion of no or unknown treatment.
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Prospective analysis of association between statin use and breast cancer risk in the womens health initiative.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-23-2013
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Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Womens Health Initiative (WHI) to assess the relationship between statins and breast cancer risk.
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Clinical and pathologic characteristics of serous carcinoma confined to the endometrium: a multi-institutional study.
Int. J. Gynecol. Pathol.
PUBLISHED: 02-02-2013
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The objective of this study was to analyze the clinical and pathologic factors in patients with uterine serous carcinoma confined to the endometrium. A total of 236 uterine serous carcinoma patients from the pathology databases of 4 large academic institutions were included in the study. Clinical and pathologic variables were analyzed, including patient demographics, tumor size (?2 vs. >2 cm), myometrial invasion, lymphovascular invasion, lymph node status, tumor location (endometrium vs. polyp), cervical involvement, lower uterine segment involvement, FIGO stage, pelvic washings, recurrence, overall survival, and progression-free survival. Of 236 patients, 55 (23%) had tumors limited to the endometrium. Forty-four patients (80%) had Stage IA tumors. The tumor was confined to a polyp in 17 (30.9%) patients. Twenty patients (36.4%) had tumor sizes >2 cm and 12 (21.8%) exhibited lymphovascular invasion. Only 3 patients (5.4 %) had cervical stromal involvement. Thirty-three (66%) patients underwent pelvic and para-aortic lymphadenectomy with 2 positive para-aortic lymph nodes identified. Seven (12.7%) patients had positive washings, whereas 8 patients (14.5 %) had disease recurrence. At a median follow-up of 46 months, there was no difference in overall survival (P = 0.216) or progression-free survival (P=0.063) between patients with tumors confined to a polyp, patients with tumors confined to the endometrium, and patients with tumors present in both polyp and the endometrium. Uterine serous carcinoma with only endometrial involvement, even when confined to a polyp, can be associated with poor prognosis, further stressing the importance of complete surgical staging and adjuvant treatment in this setting.
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An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies.
Int. J. Cancer
PUBLISHED: 01-15-2013
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To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case-control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. In case-only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4 per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell cases (N = 1,524). In case-control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m(2) increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology.
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Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-time PCR.
PLoS ONE
PUBLISHED: 01-01-2013
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Amplification of the fibroblast growth factor receptor 1 (FGFR1) gene has been described in tumors of non-small-cell lung cancer (NSCLC) patients. Prior reports showed conflicting rates of amplification frequency and clinical relevance.
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ATM mutations in patients with hereditary pancreatic cancer.
Cancer Discov
PUBLISHED: 12-29-2011
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Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition.
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Asthma and lung cancer risk: a systematic investigation by the International Lung Cancer Consortium.
Carcinogenesis
PUBLISHED: 12-22-2011
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Asthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assess this association and compared the results with 36 previously published studies. In total, information from 585?444 individuals was used. Study-specific measures were combined using random effects models. A meta-regression and subgroup meta-analyses were performed to identify sources of heterogeneity. The overall LC relative risk (RR) associated with asthma was 1.28 [95% confidence intervals (CIs) = 1.16-1.41] but with large heterogeneity (I(2) = 73%, P < 0.001) between studies. Among ILCCO studies, an increased risk was found for squamous cell (RR = 1.69, 95%, CI = 1.26-2.26) and for small-cell carcinoma (RR = 1.71, 95% CI = 0.99-2.95) but was weaker for adenocarcinoma (RR = 1.09, 95% CI = 0.88-1.36). The increased LC risk was strongest in the 2 years after asthma diagnosis (RR = 2.13, 95% CI = 1.09-4.17) but subjects diagnosed with asthma over 10 years prior had no or little increased LC risk (RR = 1.10, 95% CI = 0.94-1.30). Because the increased incidence of LC was chiefly observed in small cell and squamous cell lung carcinomas, primarily within 2 years of asthma diagnosis and because the association was weak among never smokers, we conclude that the association may not reflect a causal effect of asthma on the risk of LC.
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Clinical/pathologic features and patient outcome in early onset endometrial carcinoma: a population based analysis and an institutional perspective from the Detroit metropolitan area, Michigan.
Gynecol. Oncol.
PUBLISHED: 08-08-2011
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Analyze tumor characteristics and outcomes in patients with endometrial carcinoma (EC)<40 years of age and compare them to the characteristics of patients ? 40 years of age.
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The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients.
Clin Lung Cancer
PUBLISHED: 07-06-2011
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Airflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American population
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Trends in the utilization of adjuvant vaginal cuff brachytherapy and/or external beam radiation treatment in stage I and II endometrial cancer: a surveillance, epidemiology, and end-results study.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-11-2011
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The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time.
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Frequency and type of epidermal growth factor receptor mutations in African Americans with non-small cell lung cancer.
J Thorac Oncol
PUBLISHED: 02-15-2011
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Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict response to tyrosine kinase inhibitors. Mutations occur more commonly in never smokers and East Asians, but there are conflicting reports on the frequency of EGFR mutations in tumors from African Americans.
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The impact of race on survival in uterine serous carcinoma: a hospital-based study.
Gynecol. Oncol.
PUBLISHED: 02-01-2011
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Although less common than endometrioid carcinoma, uterine serous carcinoma (USC) accounts for a disproportionate number of endometrial cancer-related deaths. It is relatively more common in black compared to white women. The aim of our study is to analyze the impact of race on survival in USC.
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Admixture mapping of lung cancer in 1812 African-Americans.
Carcinogenesis
PUBLISHED: 11-29-2010
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Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 × 10??) and for women with NSCLC (Z-score = -4.82; P = 1.4 × 10??). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.
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Parameters for individualizing systemic therapy in non-small cell lung cancer.
Drug Resist. Updat.
PUBLISHED: 09-24-2010
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Rational drug design based on molecular targets is starting to revolutionize cancer care. To maximize its potential for patients, a concomitant leveraging of molecular knowledge for selection of patients to future and current therapeutic options is paramount. The terms "individualized", "personalized", or "precision therapy" are currently used to describe these efforts. Here, we summarize current knowledge for selection of systemic targeted and cytotoxic therapy for patients with non-small-cell lung cancer. Based on this knowledge, we present a potential decision algorithm to best select patients for currently available therapies, which include the treatment options single-agent erlotinib or gefitinib, the ALK inhibitor crizotinib, double agent gemcitabine and platinum, double agent platinum and pemetrexed, and as a default option a taxane combined with a non-platinum drug, for instance a vinca alkaloid. The addition of bevacizumab to double-agent chemotherapy is also discussed. Currently available data on predictive biomarkers are largely based on subgroup or companion biomarker analyses of patient cohorts or clinical trials. Current and emerging markers must be incorporated prospectively into the design of clinical trials that test novel and established agents to better understand their clinical utility and to refine selection parameters and marker interactions. Future development will lead to increasing complexity in clinical decision making with substantial anticipated benefits to patients including increased therapeutic efficacy, reduced toxicity, and better quality of life.
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Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the U.S.--a SEER analysis.
BMC Cancer
PUBLISHED: 05-11-2010
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Recent reports suggest increase in estrogen receptor (ER), progesterone receptor (PR) negative breast cancer yet little is known about histology or receptor status of breast cancer in Indian/Pakistani women.in the U.S.
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Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO).
Cancer Causes Control
PUBLISHED: 04-09-2010
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The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer.
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Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women.
J Cancer Epidemiol
PUBLISHED: 09-01-2009
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In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.
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Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.
J Thorac Oncol
PUBLISHED: 07-31-2009
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Three genome-wide association studies identified a region on chromosome 15q25.1 associated with lung cancer and measures of nicotine addiction. This region includes nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5. These studies were conducted in European or European American populations and do not provide risk estimates for African Americans. The goal of this study was to determine whether recently identified genetic variation in 3 SNPs (rs1051730, rs931794, rs8034191) on chromosome 15q25.1 contributes to risk of lung cancer in African Americans.
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Cytokine and cytokine receptor single-nucleotide polymorphisms predict risk for non-small cell lung cancer among women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-10-2009
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Studies on the relationships between inflammatory pathway genes and lung cancer risk have not included African-Americans and have only included a handful of genes. In a population-based case-control study on 198 African-American and 744 Caucasian women, we examined the association between 70 cytokine and cytokine receptor single-nucleotide polymorphisms (SNPs) and risk of non-small cell lung cancer (NSCLC). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals in a dominant model adjusting for major risk factors for lung cancer. Separate analyses were conducted by race and by smoking history and history of chronic obstructive pulmonary disease among Caucasians. Random forest analysis was conducted by race. On logistic regression analysis, IL6 (interleukin 6), IL7R, IL15, TNF (tumor necrosis factor), and IL10 SNP were associated with risk of non-small cell lung cancer among African-Americans; IL7R and IL10 SNPs were also associated with risk of lung cancer among Caucasians. Although random forest analysis showed IL7R and IL10 SNPs as being associated with risk for lung cancer among African-Americans, it also identified TNFRSF10A SNP as an important predictor. On random forest analysis, an IL1A SNP was identified as an important predictor of lung cancer among Caucasian women. Inflammatory SNPs differentially predicted risk for NSCLC according to race, as well as based on smoking history and history of chronic obstructive pulmonary disease among Caucasian women. Pathway analysis results are presented. Inflammatory pathway genotypes may serve to define a high risk group; further exploration of these genes in minority populations is warranted.
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Study designs in genetic epidemiology.
Methods Mol. Biol.
PUBLISHED: 04-22-2009
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Identification of germline mutations that may modulate individual risk of developing cancer is a rapidly developing field. Over the last few decades, germline mutations in p53, BRCA1, BRCA2, APC, MLH1, MSH2, and MSH6 have been identified in families with a large number of relatives who have been diagnosed with particular types of cancer. These mutations are rare but substantially increase the risk of cancer in carriers, and account for a small fraction of cancer cases diagnosed in the general population. The search for common mutations that correlate with a very modest increased risk of developing cancer is ongoing. With the completion of the Human Genome Project, a large array of methods to identify these genes and their variants are under development. The following chapter describes methods to provide evidence of a genetic component associated with disease risk, how to identify chromosomal regions of interest to identify rare but highly penetrant genetic variants, and methods used to identify more common mutations which modulate cancer development.
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Second neoplasms in survivors of endometrial cancer: impact of radiation therapy.
Gynecol. Oncol.
PUBLISHED: 02-26-2009
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To evaluate the association of radiotherapy to subsequent second cancers in endometrial carcinoma survivors.
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Meta- and pooled analysis of GSTP1 polymorphism and lung cancer: a HuGE-GSEC review.
Am. J. Epidemiol.
PUBLISHED: 02-24-2009
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Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A --> 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites.
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Chronic obstructive lung diseases and risk of non-small cell lung cancer in women.
J Thorac Oncol
PUBLISHED: 02-05-2009
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The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women.
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Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women.
Carcinogenesis
PUBLISHED: 01-27-2009
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To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.
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Impact of microsatellite instability (MSI) on survival in high grade endometrial carcinoma.
Gynecol. Oncol.
PUBLISHED: 01-26-2009
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Although microstellite instability (MSI) is a prognostic marker in colorectal cancer, its relation with prognosis in the endometrial cancer is controversial. The goal of this study is to identify the correlation between MSI and clinicopathologic markers along with survival in high grade endometrial carcinoma EC.
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Cytokine SNPs: Comparison of allele frequencies by race and implications for future studies.
Cytokine
PUBLISHED: 01-06-2009
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The role of inflammation is being considered in chronic diseases. Previous studies have examined SNPs in a few key inflammatory genes and have included small numbers of African American participants. Variation in the frequencies of inflammatory pathway SNPs may help to explain racial disparities in disease risk. Through a population-based study of 103 African American and 380 Caucasian unrelated, healthy women, we examined the relationships between race and allele frequencies of 70 cytokine and cytokine receptor SNPs. The associations between genotypic and haplotype frequencies and race were also analyzed. Allelic frequencies for 52 out of the 70 SNPs meeting criteria for analysis differed significantly by race. Of the 32 pro-inflammatory and 20 anti-inflammatory SNPs for which the allele frequencies varied significantly by race, variant allele frequency differences between Caucasians and African Americans ranged between 6-37% and 7-53% for pro-inflammatory SNPs and anti-inflammatory SNPs, respectively. Our findings suggest that while allele frequencies do vary by race, racial groups are not simplistically represented by a pro-inflammatory or anti-inflammatory genetic profile. Given the racial variability in allele frequencies in inflammatory gene SNPs, studies examining the association between these SNPs and disease should at least incorporate self-reported race in their analyses.
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A Comparison of Logistic Regression, Logic Regression, Classification Tree, and Random Forests to Identify Effective Gene-Gene and Gene-Environmental Interactions.
Int J Appl Sci Technol
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Genome wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with a variety of common human diseases. Due to the weak marginal effect of most disease-associated SNPs, attention has recently turned to evaluating the combined effect of multiple disease-associated SNPs on the risk of disease. Several recent multigenic studies show potential evidence of applying multigenic approaches in association studies of various diseases including lung cancer. But the question remains as to the best methodology to analyze single nucleotide polymorphisms in multiple genes. In this work, we consider four methods-logistic regression, logic regression, classification tree, and random forests-to compare results for identifying important genes or gene-gene and gene-environmental interactions. To evaluate the performance of four methods, the cross-validation misclassification error and areas under the curves are provided. We performed a simulation study and applied them to the data from a large-scale, population-based, case-control study.
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Benign breast disease and the risk of subsequent breast cancer in African American women.
Cancer Prev Res (Phila)
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Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted. Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21-8.93]. Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival.
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Racial differences in oncogene mutations detected in early-stage low-grade endometrial cancers.
Int. J. Gynecol. Cancer
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To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors.
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Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium.
Am. J. Epidemiol.
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To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984-2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.
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Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium.
Eur. J. Cancer
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Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals.
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The impact of race and comorbidity on survival in endometrial cancer.
Cancer Epidemiol. Biomarkers Prev.
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Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity.
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Cigarette smoking and renal cell carcinoma risk among black and white Americans: effect modification by hypertension and obesity.
Cancer Epidemiol. Biomarkers Prev.
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Incidence of kidney cancer has been increasing over the past three decades, with more rapid increases and higher incidence rates among blacks than whites in the United States. An association between cigarette smoking and renal cell carcinoma (RCC), the most common form of kidney cancer, has been reported for whites, but the association in blacks is less clear.
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HNF1B and endometrial cancer risk: results from the PAGE study.
PLoS ONE
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We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Womens Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ? 0.21) or between studies (P ? 0.70). The OR(per allele) was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6)) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7)) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P ? 0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.
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Outcomes of patients with uterine serous carcinoma using the revised FIGO staging system.
Int. J. Gynecol. Cancer
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Our aim was to evaluate the prognostic significance of the revised 2009 International Federation of Gynecology and Obstetrics (FIGO) staging criteria in patients with uterine serous carcinoma (USC).
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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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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.