Redefining precision cancer prevention to promote health equity.

Precision cancer prevention as it is currently envisioned is a targeted, molecular-based approach to intercept carcinogenesis before cancer develops or before it becomes untreatable. Unfortunately, due to systemic biases, current precision cancer prevention interventions might not be effective in all populations, especially in minoritized communities. In addition, not all cancer risk is attributable to genetic or even biological factors, but includes social determinants of health (SDH).

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC).

Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality.

This study evaluates the association of inflammation in late adolescence as measured by erythrocyte sedimentation rate with cause-specific mortality among healthy Swedish men assessed for conscription in the military.

Socioenvironmental adversity and risk of prostate cancer in non-Hispanic black and white men.

Non-Hispanic black (NHB) men experience higher risk of prostate cancer than other racial/ethnic groups, and it is possible that socioenvironmental (SE) adversity and resulting stress may contribute to this disparity. Data from the Southern Community Cohort Study were used to evaluate associations between SE adversity and perceived stress in relation to prostate cancer risk, overall and by race/ethnicity and grade. Between 2002 and 2009, 26,741 men completed a questionnaire, from which an 8-item SE adversity composite was created (covering socioeconomic status, residential environment, and social support/buffers).

Allergies and Asthma in Relation to Cancer Risk.

Background: Allergies and asthma, conditions commonly characterized by immunoglobulin E-mediated atopic reactions, may decrease cancer risk via increases in immunosurveillance, but may increase risk due to persistent immune stimulation. Associations between allergies and asthma and cancer risk remain unclear, and it is unknown whether associations vary by race/ethnicity.

Methods: We evaluated these associations in the Southern Community Cohort Study.

Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.

Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.

Built Environment and Depression in Low-Income African Americans and Whites.

Introduction: Urban environments are associated with a higher risk of adverse mental health outcomes; however, it is unclear which specific components of the urban environment drive these associations.

Methods: Using data collected in 2002-2009 from 73,225 low-income, racially diverse individuals across the Southeastern U.S.

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.

Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.

Results: We found that variants in 7p15.

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.

Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression.

Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study.

Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred.

Sleep duration and breast cancer risk among black and white women.

Background: Sleep has been suggested to influence breast cancer risk; however, the evidence is mixed. Black women have a higher prevalence of both short (<6 h) and long (≥9 h) sleep duration and are more likely to develop more aggressive, hormone receptor-negative breast cancer. No study has examined the relationship between sleep and breast cancer in blacks.

A prospective study of Trichomonas vaginalis and prostate cancer risk among African American men.

Background: African Americans (AA) have a higher prevalence of Trichomonas vaginalis (Tv) infection and a higher prostate (PC) risk. Past studies suggest an association between Tv seropositivity and PC, and therefore we prospectively investigated this association among AA men.

Results: Incident PC cases were individually matched to controls in a nested case-control study within the Southern Community Cohort Study (SCCS).

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines.

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.

Persistence of Trichomonas vaginalis serostatus in men over time.

Purpose: Previous epidemiologic studies have observed positive associations between Trichomonas vaginalis (Tv) serostatus and both prostate cancer (PCa) risk and mortality. However, only a few small older studies have examined Tv antibody persistence over time, all of which were composed mainly of female patients. Therefore, we examined Tv antibody persistence over time, as well as intra-individual variability, among middle- to older-aged men in the Southern Community Cohort Study (SCCS).

Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry.

Physical activity, sedentary behavior and all-cause mortality among blacks and whites with diabetes.

Purpose: The study objective was to examine the role of physical activity (PA) and sedentary time (ST) on mortality risk among a population of low-income adults with diabetes.

Methods: Black (n = 11,137) and white (n = 4508) men and women with diabetes from the Southern Community Cohort Study self-reported total PA levels and total ST. Participants were categorized into quartiles of total PA and total ST.

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants.

Statin use and risk of prostate cancer: Results from the Southern Community Cohort Study.

Background: Epidemiologic studies suggest that statin use may be inversely associated with risk of prostate cancer, but prior studies have focused predominantly on non-Hispanic white populations.

Methods: We evaluated the association between statin use and prostate cancer risk in the Southern Community Cohort Study (SCCS). Study participants were 32,091 men aged 40-79 at baseline, 67% of whom were non-Hispanic black.

Healthy Eating and Risks of Total and Cause-Specific Death among Low-Income Populations of African-Americans and Other Adults in the Southeastern United States: A Prospective Cohort Study.

Background: A healthy diet, as defined by the US Dietary Guidelines for Americans (DGA), has been associated with lower morbidity and mortality from major chronic diseases in studies conducted in predominantly non-Hispanic white individuals. It is unknown whether this association can be extrapolated to African-Americans and low-income populations.

Methods And Findings: We examined the associations of adherence to the DGA with total and cause-specific mortality in the Southern Community Cohort Study, a prospective study that recruited 84,735 American adults, aged 40-79 y, from 12 southeastern US states during 2002-2009, mostly through community health centers that serve low-income populations.

Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk.

Objective: Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16-20 years).

Design: At the time of the conscription assessment (1969-1976), height and weight were measured and ESR was assayed.

Body mass index in young adulthood, obesity trajectory, and premature mortality.

Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40-79 years and were followed through December, 2011.

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry.

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2.

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.