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Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.


ABSTRACT: BACKGROUND:Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS:To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS:Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS:These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. IMPACT:These results might provide some clues for the strong link between 8q24 and prostate cancer risk.

SUBMITTER: Chu LW 

PROVIDER: S-EPMC2901401 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.

Chu Lisa W LW   Meyer Tamra E TE   Li Qizhai Q   Menashe Idan I   Yu Kai K   Rosenberg Philip S PS   Huang Wen-Yi WY   Quraishi Sabah M SM   Kaaks Rudolf R   Weiss Jocelyn M JM   Hayes Richard B RB   Chanock Stephen J SJ   Hsing Ann W AW  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100615 7


<h4>Background</h4>Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.<h4>Methods</h4>To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and se  ...[more]

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