A common 8q24 variant in prostate and breast cancer from a large nested case-control study.

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
Cancer Research (Impact Factor: 9.28). 05/2007; 67(7):2951-6. DOI: 10.1158/0008-5472.CAN-06-3591
Source: PubMed

ABSTRACT Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 x 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an OR(AC) = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an OR(AA) = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result.

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    ABSTRACT: Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (PCa). As PCa risk SNPs may also influence disease outcome, we studied here eight 8q24 risk alleles, and evaluated their role in PCa clinical covariates in northern Chinese men. Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=289) and from age-matched normal controls (n=288). Eight 8q24 SNPs were genotyped by polymerase chain reaction- high-resolution melting analysis in 577 subjects. We examined the prevalence distribution of 8q24 risk alleles and analyzed the associations between the risk allele and PCa and clinical covariates to infer their impact on aggressive PCa. Three of the eight SNPs were associated with PCa risk in northern Chinese men, including rs16901966 (OR 1.31, 95% CI 1.01-1.70, p=0.042), rs1447295 (OR 1.47, 95% CI 1.09-1.98, p=0.011) and rs10090154 (OR 1.55, 95% CI 1.14-2.12, p=0.005). Haplotype analysis based association with the risk alleles revealed significant differences between cases and controls (OR 1.43, 95%CI 0.99-2.06, p=0.049). The risk alleles rs16901966, rs1447295 and rs10090154 were associated with age at diagnosis and tumor stage as compared with controls, while rs16901966 was associated with aggressive PCa (OR 1.43, 95% CI 1.01-2.03, p=0.042). The evidence for 8q24 SNPs with PCa risk in northern Chinese men showed rs16901966, rs1447295 and rs10090154 at 8q24 (region 1, region 2) to be strongly associated with PCa and clinical covariates. The three SNPs at 8q24 could be PCa susceptible genetic markers in northern Chinese men.
    Asian Pacific journal of cancer prevention: APJCP 11/2013; 14(11):6733-8. DOI:10.7314/APJCP.2013.14.11.6733 · 1.50 Impact Factor
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    ABSTRACT: BACKGROUND African American men (AA) exhibit a disproportionate share of prostate cancer (PRCA) incidence, morbidity, and mortality. Several genetic association studies have implicated select 8q24 loci in PRCA risk in AA. The objective of this investigation is to evaluate the association between previously reported 8q24 risk alleles and PRCA in African-Barbadian (AB) men known to have high rates of PRCA.METHODS Ten previously reported candidate tag SNPs were genotyped and/or imputed in the 8q24 region in 532 AB men with PRCA and 513 AB controls from the Prostate Cancer in a Black Population (PCBP) study.RESULTSRs2124036 was significant in AB men, (OR = 2.7, 95% CI (1.3–5.3), P = 0.005, Empirical (max (T), corrected for multiple testing) P = 0.03) for the homozygous C/C genotype. Only a single SNP from this region remained statistically significant in our analysis of our AB population. These results may indicate the presence of a founder effect or due to the chosen SNPs not tagging an ancestral haplotype bearing the 8q24 risk allele(s) in this population or could reflect inadequate power to detect an association. We conducted a meta-analysis including our AB population along with two additional African Caribbean populations from Tobago and Jamaica for SNPs rs16901979 and rs1447295. Meta-analysis results were most significant for rs16901979 A allele (Z score 2.73; P = 0.006) with a summary OR = 1.31 (95% CI: 1.09–1.58).CONCLUSIONS Additional studies are needed to provide deeper genotype coverage to further interrogate the 8q24 region to understand its contribution to PRCA in this population. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 12/2014; 74(16). DOI:10.1002/pros.22871 · 3.57 Impact Factor
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    ABSTRACT: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations.
    Asian Pacific journal of cancer prevention: APJCP 10/2014; 15(19):8311-7. DOI:10.7314/APJCP.2014.15.19.8311 · 1.50 Impact Factor


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