Dataset Information

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men.

ABSTRACT: Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48-0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10?³). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.

SUBMITTER: Gu CY

PROVIDER: S-EPMC4236333 | biostudies-literature | 2014 Nov-Dec

REPOSITORIES: biostudies-literature

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Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men.

Gu Cheng-Yuan CY Li Qiao-Xin QX Zhu Yao Y Wang Meng-Yun MY Shi Ting-Yan TY Yang Ya-Yun YY Wang Jiu-Cun JC Jin Li L Wei Qing-Yi QY Ye Ding-Wei DW

Asian journal of andrology 20141101 6

Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymera ...[more]

PMID: 25038177

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Project description:BACKGROUND:Men of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population. METHODS:We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men. Unconditional logistic regression was used to test genetic associations and a polygenic risk score (PRS) was derived to assess the cumulative effect of the known risk alleles in association with PCa risk. In an exploratory analysis, we also tested associations of 17?125?421 genotyped and imputed markers genome-wide in association with PCa risk. RESULTS:Of the 111 known risk loci with a frequency >1%, 75 (68%) had effects that were directionally consistent with the initial discovery population,14 (13%) of which were nominally significantly associated with PCa risk at P?<?0.05. Compared to men with average risk (25th -75th percentile in PRS distribution), Ugandan men in the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to 4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome-wide association testing, the strongest associations were noted with known risk alleles located in the 8q24 region, including rs72725854 (OR?=?3.37, P?=?2.14?×?10-11 ) that is limited to populations of African ancestry (6% frequency). CONCLUSIONS:The ?100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.

Dataset Information

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men.

Publications

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men.

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