Dataset Information

Association between sequence variants at 17q12 and 17q24.3 and prostate cancer risk in European and African Americans.

ABSTRACT: Three SNPs at 17q12 and four SNPs at 17q24.3 were recently identified to be associated with prostate cancer risk using a genome-wide association study.We evaluated these 7 SNPs in two hospital-based case-control study populations, including European Americans (EA; 1,563 cases and 576 controls) and African Americans (AA; 364 cases and 353 controls).Each of the reported risk alleles of these seven SNPs were more common in cases than in controls among EA and AA. The differences were highly significant in EA (P = 10(-4)) and marginally significant in AA (P = 0.04) for SNPs at 17q12. In contrast, the differences were not statistically significant in EA or AA for SNPs at 17q24.3, but were marginally significant for two SNPs (P = 0.04-0.06) when EA and AA subjects were combined. Similar results were obtained when genotype and haplotype frequencies between cases and controls were analyzed. These risk variants were not associated with more aggressive prostate cancer or other clinical variables such as TNM stage, pre-operative PSA, or age at diagnosis.Results from our study provide the first confirmation of these 17q SNPs as novel prostate cancer susceptibility loci in EA and the first indication that these two loci may also play roles in prostate cancer risk among AA.

SUBMITTER: Sun J

PROVIDER: S-EPMC3176499 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Association between sequence variants at 17q12 and 17q24.3 and prostate cancer risk in European and African Americans.

Sun Jielin J Purcell Lina L Gao Zhengrong Z Isaacs Sarah D SD Wiley Kathleen E KE Hsu Fang-Chi FC Liu Wennuan W Duggan David D Carpten John D JD Grönberg Henrik H Xu Jianfeng J Chang Bao-Li BL Partin Alan W AW Walsh Patrick C PC Isaacs William B WB Zheng S Lilly SL

The Prostate 20080501 7

<h4>Background</h4>Three SNPs at 17q12 and four SNPs at 17q24.3 were recently identified to be associated with prostate cancer risk using a genome-wide association study.<h4>Methods</h4>We evaluated these 7 SNPs in two hospital-based case-control study populations, including European Americans (EA; 1,563 cases and 576 controls) and African Americans (AA; 364 cases and 353 controls).<h4>Results</h4>Each of the reported risk alleles of these seven SNPs were more common in cases than in controls am ...[more]

PMID: 18361410

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Project description:The prevalence of type 2 diabetes (T2D) is greater in populations of African descent compared to European-descent populations. Genetic risk factors may underlie the disparity in disease prevalence. Genome-wide association studies (GWAS) have identified >60 common genetic variants that contribute to T2D risk in populations of European, Asian, African and Hispanic descent. These studies have not comprehensively examined population differences in cumulative risk allele load. To investigate the relationship between risk allele load and T2D risk, 46 T2D single nucleotide polymorphisms (SNPs) in 43 loci from GWAS in European, Asian, and African-derived populations were genotyped in 1,990 African Americans (n = 963 T2D cases, n = 1,027 controls) and 1,644 European Americans (n = 719 T2D cases, n = 925 controls) ascertained and recruited using a common protocol in the southeast United States. A genetic risk score (GRS) was constructed from the cumulative risk alleles for each individual. In African American subjects, risk allele frequencies ranged from 0.024 to 0.964. Risk alleles from 26 SNPs demonstrated directional consistency with previous studies, and 3 SNPs from ADAMTS9, TCF7L2, and ZFAND6 showed nominal evidence of association (p < 0.05). African American individuals carried 38-67 (53.7 ± 4.0, mean ± SD) risk alleles. In European American subjects, risk allele frequencies ranged from 0.084 to 0.996. Risk alleles from 36 SNPs demonstrated directional consistency, and 10 SNPs from BCL11A, PSMD6, ADAMTS9, ZFAND3, ANK1, CDKN2A/B, TCF7L2, PRC1, FTO, and BCAR1 showed evidence of association (p < 0.05). European American individuals carried 38-65 (50.9 ± 4.4) risk alleles. African Americans have a significantly greater burden of 2.8 risk alleles (p = 3.97 × 10(-89)) compared to European Americans. However, GRS modeling showed that cumulative risk allele load was associated with risk of T2D in European Americans, but only marginally in African Americans. This result suggests that there are ethnic-specific differences in genetic architecture underlying T2D, and that these differences complicate our understanding of how risk allele load impacts disease susceptibility.

Project description:To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs).Cross-sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (?) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle-brachial index, race (site), and supported interactions.Genetic Epidemiology Network of Arteriopathy-Genetics of Microangiopathic Brain Injury Study cohort.AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26-91, 50% obese, 72% hypertensive).Inflammation (C-reactive protein (CRP), interleukin-6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm(3) ) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self-reported difficulty walking half a mile).In separate models, inflammatory markers were associated with walking speed (sTNFR1: ? = -2.74, P < .001; sTNFR2: ? = -1.23, P = .03; CRP: ? = -1.95, P = .001; IL6: ? = -1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (? = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (? = -3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations.In young, middle-aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.

Dataset Information

Association between sequence variants at 17q12 and 17q24.3 and prostate cancer risk in European and African Americans.

Publications

Association between sequence variants at 17q12 and 17q24.3 and prostate cancer risk in European and African Americans.

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