Setiawan Veronica Wendy, Doherty Jennifer A, Shu Xiao-Ou, Akbari Mohammad R, Chen Chu, De Vivo Immaculata, Demichele Angela, Garcia-Closas Montserrat, Goodman Marc T, Haiman Christopher A, Hankinson Susan E, Henderson Brian E, Horn-Ross Pamela L, Lacey James V, Le Marchand Loic, Levine Douglas A, Liang Xiaolin, Lissowska Jolanta, Lurie Galina, McGrath Monica, Narod Steven A, Rebbeck Timothy R, Ursin Giske, Weiss Noel S, Xiang Yong-Bing, Yang Hannah P, Zheng Wei, Olson Sara H
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):242-7. doi: 10.1158/1055-9965.EPI-08-0689.
Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 x 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age >or=55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >or=55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women.
细胞色素P450 19A1（CYP19A1）中的常见变异（rs749292和rs727479的A等位基因）与绝经后女性循环雌激素水平升高10%至20%有关。我们假设这些单核苷酸多态性（SNP）中一个或两个A等位基因的存在与子宫内膜癌风险增加有关。我们在子宫内膜癌联盟流行病学的10项研究中对4998例子宫内膜癌病例和8285例对照进行的大型汇总分析中检验了这一假设。大多数女性（>66%）为白人，该汇总分析中也纳入了较小比例的其他种族和族裔群体（黑人、亚洲人和拉丁裔）。采用无条件逻辑回归对SNP/单倍型与子宫内膜癌风险之间的关联进行建模。携带这两个SNP中任何一个的A等位基因均与子宫内膜癌风险增加有关，rs749292每个等位基因的合并比值比为1.14，95%置信区间为1.09 - 1.21，P = 7.1×10⁻⁷；rs727479每个等位基因的比值比为1.08，95%置信区间为1.02 - 1.14，P = 0.009。对于rs749292，这些关联在年龄≥55岁的女性中通常更强。对于这两个SNP，风险均随体重指数增加而升高，对于rs727479，这种模式在年龄≥55岁的女性中似乎更强（P相互作用 = 0.007）。通过直接计数或单倍型分析，两个SNP中A等位基因的组合并未使风险增加超过单个SNP所观察到的风险。我们的研究提供了证据表明CYP19A1基因变异会影响子宫内膜癌的易感性，尤其是在老年和肥胖女性中。
