Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11α in prostate cancer risk and aggressiveness
Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11α in prostate cancer risk and aggressiveness
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DOI：
10.1158/1055-9965.epi-05-0215
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发表时间：
2005-09-01
影响因子：
3.8
通讯作者：
Witte, JS
中科院分区：
文献类型：
--
作者：
Cicek, MS;Liu, X;Witte, JS
与雄激素代谢有关的候选基因被认为会影响前列腺癌的风险。为了进一步研究这一点，我们评估了与雄激素代谢有关的三个基因的多个潜在功能多态与前列腺癌的关系：CYP1B1(两个单核苷酸多态：355G/T和4326C/G)、前列腺特异性抗原(PSA/KLK3)(三个单核苷酸多态：-15SA/G、-4643G/IA和-5412C/T)和CYP11α[(Ttta)(N)重复]，采用中等规模(n=918)以同胞为基础的病例对照人群。当综合观察所有受试者时，没有观察到任何多态或他们的单倍型与前列腺癌风险之间的关联。然而，在更具侵袭性的前列腺癌患者中，携带一个或两个T等位基因的优势比(OR)分别为1.9[95%可信区间(95%CI)，1.09~3.31；P=0.02]和3.73(95%CI，1.39~10.0；P=0.009)。同样，在患有高侵袭性疾病的男性中，携带CYP1B1355T-4326C单倍型与前列腺癌呈正相关(P=0.01)。此外，在疾病侵袭性较弱的男性中，PSA-158G/-158G基因型与前列腺癌呈正相关(OR，2.71；95%CI，1.06~6.94；P=0.04)。我们的发现表明，CYP1B1和PSA变异可能会影响前列腺癌和肿瘤侵袭性的风险。
Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: -15SA/G, -4643G/I A, and -5412C/T), and CYP11 alpha [(tttta)(n) repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism-or their haplotypes and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA -158G/-158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% Cl, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.