Discordance between self-report and genetic confirmation of sickle cell disease status in African-American adults.

Background: Sickle cell disease (SCD) is an autosomal recessive genetic disorder, with persons heterozygous for the mutation said to have the sickle cell trait (SCT). Serious adverse effects are mainly limited to those with SCD, but the distinction between disease and trait is not always clear to the general population. We sought to determine the accuracy of self-reported SCD when compared to genetic confirmation.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk.

Plasma selenium biomarkers in low income black and white americans from the southeastern United States.

Biomarkers of selenium are necessary for assessing selenium status in humans, since soil variation hinders estimation of selenium intake from foods. In this study, we measured the concentration of plasma selenium, selenoprotein P (SEPP1), and glutathione peroxidase (GPX3) activity and their interindividual differences in 383 low-income blacks and whites selected from a stratified random sample of adults aged 40-79 years, who were participating in a long-term cohort study in the southeastern United States (US). We assessed the utility of these biomarkers to determine differences in selenium status and their association with demographic, socio-economic, dietary, and other indicators.

Stage-adjusted lung cancer survival does not differ between low-income Blacks and Whites.

Introduction: Few lung cancer studies have focused on lung cancer survival in underserved populations. We conducted a prospective cohort study among 81,697 racially diverse and medically underserved adults enrolled in the Southern Community Cohort Study throughout an 11-state area of the Southeast from March 2002 to September 2009.

Methods: Using linkages with state cancer registries, we identified 501 incident non-small-cell lung cancer cases.

A prospective study of statin use and mortality among 67,385 blacks and whites in the Southeastern United States.

Purpose: The primary objective of this study is to examine the race-specific associations between statin use and overall mortality, as well as cardiovascular and cancer mortality, among blacks and whites in the Southeastern United States (US). Little is known about these associations in blacks.

Patients And Methods: The Southern Community Cohort Study is an ongoing, prospective cohort study, which enrolled from 2002 through 2009 nearly 86,000 participants aged 40-79 years.

Factors associated with the prevalence of hypertension in the southeastern United States: insights from 69,211 blacks and whites in the Southern Community Cohort Study.

Background: Lifestyle and socioeconomic status have been implicated in the prevalence of hypertension; thus, we evaluated factors associated with hypertension in a cohort of blacks and whites with similar socioeconomic status characteristics.

Methods And Results: We evaluated the prevalence and factors associated with self-reported hypertension (SR-HTN) and ascertained hypertension (A-HTN) among 69,211 participants in the Southern Community Cohort Study. Multivariable logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with hypertension.

Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1.

The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus.

Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancers: classification tree analysis.

Purpose: Although risk factors for squamous cell carcinoma of the esophagus and adenocarcinomas of the esophagus (EA), gastric cardia (GC), and other (noncardia) gastric (OG) sites have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancers.

Methods: We used classification tree analysis to analyze data from a population-based case-control study (1095 cases, 687 controls) conducted in Connecticut, New Jersey, and western Washington State.

The Björk-Shiley convexo-concave heart valve experience from the perspective of the supervisory panel.

The 20-year activities of a medical supervisory panel appointed under the terms of a settlement agreement of the Bowling v. Pfizer class action suit involving the Björk-Shiley convexo-concave (BSCC) heart valve are detailed. Of approximately 86,000 valves implanted, catastrophic failure of the valve was reported in 663 patients from 1978 to 2012.

Helicobacter pylori protein-specific antibodies and risk of colorectal cancer.

Background: There is biologic plausibility as to why infection with Helicobacter pylori, the leading cause of gastric cancer, may also increase the risk of colorectal cancer, but the epidemiologic findings have been inconsistent. We assessed the association of H. pylori protein-specific infection and colorectal cancer risk in the prospective cohort, the Southern Community Cohort Study.

Intraindividual variation in one-carbon metabolism plasma biomarkers.

Interest in the relationship between one-carbon metabolism (OCM) and carcinogenesis is intensifying, leading to increased use of related biomarkers as measures of exposure. Little is known, however, about the intraindividual variation in these markers and whether or not the use of a single measure is appropriate for assessing exposure-disease relationships in epidemiologic studies. We evaluated the intraindividual variation in plasma concentrations of 19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white participants from the Southern Community Cohort Study who donated blood samples and responded to questionnaires at two time points from 2005 to 2008.

Diabetes and prostate cancer screening in black and white men.

Purpose: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening.

Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans.

Genome-wide association studies of colorectal cancer (CRC) in Europeans and Asians have identified 21 risk susceptibility regions [29 index single-nucleotide polymorphisms (SNPs)]. Characterizing these risk regions in diverse racial groups with different linkage disequilibrium (LD) structure can help localize causal variants. We examined associations between CRC and all 29 index SNPs in 6597 African Americans (1894 cases and 4703 controls).

Mortality by race among low-income adults with early-onset insulin-treated diabetes.

Objective: To determine if long-term mortality rates in early-onset insulin-treated diabetes differ by race among adults of similar socioeconomic status.

Research Design And Methods: A total of 391 (299 African Americans, 92 whites) mostly low-income adults 40-79 years of age with insulin-treated diabetes diagnosed before 30 years of age were recruited from community health centers in the southeast U.S.

Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.

Genome-wide association studies (GWAS), conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls), recruited in the Southern Community Cohort Study (SCCS) and the Nashville Breast Health Study (NBHS).

A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry.

Sedentary behavior, physical activity, and likelihood of breast cancer among Black and White women: a report from the Southern Community Cohort Study.

Increased physical activity has been shown to be protective for breast cancer although few studies have examined this association in Black women. In addition, limited evidence to date indicates that sedentary behavior may be an independent risk factor for breast cancer. We examined sedentary behavior and physical activity in relation to subsequent incident breast cancer in a nested case-control study within 546 cases (374 among Black women) and 2,184 matched controls enrolled in the Southern Community Cohort Study.

Sedentary and physically active behavior patterns among low-income African-American and white adults living in the southeastern United States.

Increased sedentary behavior and lack of physical activity are associated with increased risk for many chronic diseases. Differences in leisure-time physical activity between African American and white adults have been suggested to partially explain racial disparities in chronic disease outcomes, but expanding the definition of physical activity to include household and occupational activities may reduce or even eliminate racial differences in total physical activity. The objective of this study was to describe patterns of active and sedentary behaviors in black and white adults and to examine these behaviors across demographic measures.

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS).

Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)).

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping.

A small number of candidate gene SNPs reveal continental ancestry in African Americans.

Using genetic data from an obesity candidate gene study of self-reported African Americans and European Americans, we investigated the number of Ancestry Informative Markers (AIMs) and candidate gene SNPs necessary to infer continental ancestry. Proportions of African and European ancestry were assessed with STRUCTURE (K = 2), using 276 AIMs. These reference values were compared to estimates derived using 120, 60, 30, and 15 SNP subsets randomly chosen from the 276 AIMs and from 1144 SNPs in 44 candidate genes.