Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.
Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.
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DOI：
10.1158/1055-9965.epi-10-0101
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
Hsing AW
中科院分区：
文献类型：
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作者：
Chu LW;Meyer TE;Li Q;Menashe I;Yu K;Rosenberg PS;Huang WY;Quraishi SM;Kaaks R;Weiss JM;Hayes RB;Chanock SJ;Hsing AW
全基因组关联研究已确定染色体 8q24 上的多个独立区域与前列腺癌、乳腺癌、结肠癌和膀胱癌相关。为了研究其生物学基础，我们检查了 563 名健康、男性患者的 8q24 风险区域中 164 个单核苷酸多态性 (SNP)（跨度为 128,101,433–128,828,043 bp）与血清雄激素（睾酮、雄烯二酮、3α二醇 G 和生物可利用睾酮）和性激素结合球蛋白水平之间的可能关联。来自前瞻性队列研究、前列腺癌、肺癌、结直肠癌和卵巢癌 (PLCO) 癌症筛查试验的非西班牙裔白人男性（55-74 岁）。使用年龄调整的线性回归模型来确定加性遗传模型中的 SNP 与对数转换的生物标志物水平之间的关联。前列腺癌风险区域 2 着丝粒的三个相邻 SNP（rs12334903、rs1456310 和 rs980171）与睾酮 (P<1.1×10−3) 和生物可利用睾酮 (P<6.3×10−4) 相关。前列腺癌风险区域 1 和雄烯二酮中的 9 个 SNP 簇存在提示性关联（P<0.05）。这些初步发现需要在更大规模的研究中得到证实，但提出了一个有趣的假设，即 8q24 癌症风险区域的遗传变异可能与雄激素水平相关。这些结果可能为 8q24 与前列腺癌风险之间的密切联系提供一些线索。
Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphism (SNPs) in the 8q24 risk regions, spanning 128,101,433–128,828,043 bp, and serum androgen (testosterone, androstenedione, 3αdiol 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 (PLCO) 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. Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P<1.1×10−3) and bioavailable testosterone (P<6.3×10−4). Suggestive associations were seen for a cluster of 9 SNPs in prostate cancer risk region 1 and androstenedione (P<0.05). These preliminary findings require confirmation in larger studies, but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions may correlate with androgen levels. These results may provide some clues for the strong link between 8q24 and prostate cancer risk.