In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4735-4735
Abstract:
Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. Recently genome-wide association studies of these two diseases have identified a single risk allele at the HNF1B locus that is associated with both diseases along with two risk loci (JAZF1 and THADA) that have been associated with both diseases through distinct unlinked variants. We, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, explored the hypothesis that common genetic variation may explain, in part, the inverse association between type II diabetes and prostate cancer, by examining known diabetes risk variants for their association with prostate cancer. Our study consists of men from a prostate cancer case-control set of 2,707 cases and 2,438 controls from five racial-ethnic groups (African American, European American, Latino, Japanese American, and Native Hawaiian) of the Multiethnic Cohort. The allelic discrimination assay was used to genotype 21 diabetes risk variants from 18 loci identified by genome-wide association studies. Unconditional logistic regression was used to examine these alleles for association with prostate cancer risk. In ethnic-pooled analysis, we did not find evidence of an association with prostate cancer for the diabetes risk alleles in either of the two loci previously associated with prostate cancer (JAZF1, rs864745, OR 1.01, 95% CI 0.92-1.10; THADA, rs7578597, OR 1.11, 95% CI 0.97-1.27). An allele (rs7961581) in the TSPAN8 locus, which has been shown to be positively associated with diabetes risk had a protective association with prostate cancer at a nominally statistically significant level (OR 0.88, 95% CI 0.80-0.97, p=7.8×10-3). Except for the risk allele at HNF1B (allele G of rs4430796), which we previously reported to be associated inversely with prostate cancer, we found no evidence of an association with prostate cancer for the diabetes risk loci at JAZF1 and THADA despite other independent alleles at these loci being associated with prostate cancer. In summary, we found an association between the TSPAN8 allele and prostate cancer risk that needs to be replicated in larger populations. Resequencing and fine-mapping studies to identify causal alleles in large association studies will be important in exploring the role of common risk variants in the inverse association between diabetes and prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4735.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-4735
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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