Setiawan Veronica Wendy, Hankinson Susan E, Colditz Graham A, Hunter David J, De Vivo Immaculata
Channing Laboratory, Department of Epidemiology, Harvard School of Public Health 677 Huntington Avenue, Boston, MA 02115, USA.
Cancer Causes Control. 2004 Aug;15(6):627-33. doi: 10.1023/B:CACO.0000036170.28502.5f.
We hypothesized that variations in the ESR2 gene may influence estrogen exposure in the uterus and thus influence endometrial cancer risk. We validated and screened for variants in the ESR2 gene and examined whether they are associated with endometrial cancer risk.
We resequenced the promoter and coding regions of the ESR2 gene in 24 endometrial cancer cases, and genotyped the validated/discovered SNPs and intronic dinucleotide CA repeat in a nested case-control study of endometrial cancer (cases = 222, controls = 666) in the Nurses' Health Study (NHS). We also explored statistical interaction between ESR2 genotypes and body mass index (BMI) or hormone replacement therapy (HRT) use among postmenopausal women and cancer risk.
Two SNPs were validated [rs1256049 in exon 5 (allelic frequencies = 98% G, 2% A) and rs1271572 in the promoter region (allelic frequencies = 60% G, 40% T)]. After adjusting for potential confounders, we observed no association between ESR2 gene polymorphisms and endometrial cancer risk [rs1256049 (OR = 1.2; 95%CI: 0.7-2.3), rs1271572 (OR = 0.8; 95%CI: 0.5-1.1) and CA repeat (22 repeat allele versus > or = 22 repeat allele, OR = 1.1; 95%CI: 0.7-1.7)]. We also did not observe any significant effect modification of the ESR2 polymorphisms by BMI or HRT use among postmenopausal women.
Our results indicate that ESR2 polymorphisms may not be associated with endometrial cancer risk.
我们推测雌激素受体2（ESR2）基因变异可能影响子宫内雌激素暴露，进而影响子宫内膜癌风险。我们对ESR2基因变异进行验证和筛选，并研究其与子宫内膜癌风险的相关性。
我们对24例子宫内膜癌病例的ESR2基因启动子和编码区进行重测序，并在护士健康研究（NHS）的子宫内膜癌巢式病例对照研究（病例=222例，对照=666例）中对验证/发现的单核苷酸多态性（SNP）和内含子二核苷酸CA重复序列进行基因分型。我们还探讨了绝经后女性ESR2基因分型与体重指数（BMI）或激素替代疗法（HRT）使用之间的统计学交互作用及其与癌症风险的关系。
验证了两个SNP [外显子5中的rs1256049（等位基因频率=98%G，2%A）和启动子区域中的rs1271572（等位基因频率=60%G，40%T）]。在调整潜在混杂因素后，我们未观察到ESR2基因多态性与子宫内膜癌风险之间存在关联[rs1256049（比值比=1.2；95%置信区间：0.7-2.3），rs1271572（比值比=0.8；95%置信区间：0.5-1.1）和CA重复序列（22次重复等位基因与≥22次重复等位基因相比，比值比=1.1；95%置信区间：0.7-1.7）]。我们也未观察到绝经后女性中BMI或HRT使用对ESR2基因多态性有任何显著的效应修饰作用。
我们的结果表明，ESR2基因多态性可能与子宫内膜癌风险无关。
