Department of Epidemiology, American Cancer Society, Atlanta, Georgia 30303-1002, USA.
Prostate. 2010 May 1;70(6):601-7. doi: 10.1002/pros.21094.
Epidemiologic studies have shown that men with type II diabetes have a lower risk of prostate cancer than non-diabetic men. Recently, common variants in two genes, HNF1B and JAZF1, were found to be associated with both of these diseases.
We examined whether the relationship between HNF1B and JAZF1 variants and decreased prostate cancer risk may potentially be mediated through diabetes in two large prospective studies, the Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes. The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. All five SNP-prostate cancer relationships did not substantially differ when the analyses were stratified by diabetic status or when diabetic status was controlled for in the model. Furthermore, the association of diabetes with prostate cancer was not altered when the SNPs were included in the logistic model.
These findings indicate that the HNF1B variants are directly associated with both diabetes and prostate cancer, that diabetes does not mediate these gene variant-prostate cancer relationships, and the relationship between these diseases is not mediated through these gene variants.
流行病学研究表明,2 型糖尿病男性患前列腺癌的风险低于非糖尿病男性。最近,两个基因(HNF1B 和 JAZF1)的常见变体被发现与这两种疾病都有关。
我们在两项大型前瞻性研究中,即癌症预防研究 II 营养队列和前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中,检查了 HNF1B 和 JAZF1 变体与降低前列腺癌风险之间的关系是否可能通过糖尿病来介导。
三个 HNF1B SNPs(rs11649743、rs4430796 和 rs7501939)与前列腺癌风险降低有关,与糖尿病风险增加也有一定的统计学意义。JAZF1 SNPs(rs6968704 和 rs10486567)与前列腺癌风险降低有关,但与糖尿病无关。当按糖尿病状态分层或在模型中控制糖尿病状态时,所有五个 SNP-前列腺癌关系都没有显著差异。此外,当将这些 SNP 纳入逻辑回归模型时,糖尿病与前列腺癌的关联并没有改变。
这些发现表明,HNF1B 变体与糖尿病和前列腺癌都有直接关系,糖尿病不能介导这些基因变异与前列腺癌之间的关系,这些疾病之间的关系也不是通过这些基因变异来介导的。