Xu Wang-Hong, Long Ji-Rong, Zheng Wei, Ruan Zhi-Xian, Cai Qiuyin, Cheng Jia-Rong, Xiang Yong-Bing, Shu Xiao-Ou
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China.
Cancer. 2009 Jun 15;115(12):2693-700. doi: 10.1002/cncr.24289.
Single nucleotide polymorphisms (SNPs) in the progesterone receptor (PGR) gene have been associated with the risk of endometrial cancer. However, to the authors' knowledge, no study to date has systematically evaluated the role of the PGR gene in endometrial carcinogenesis.
Exposure information and DNA samples collected in the Shanghai Endometrial Cancer Study, a population-based case-control study of 1,204 incident cases and 1,212 age- and frequency-matched population controls, were used in this study. Seven tag SNPs were identified for the PGR gene plus the 5-kilobase (kb) flanking regions using the Han Chinese data from the HapMap project with a pairwise correlation coefficient (r(2)) >or= 0.90. These 7 SNPs captured 92% of SNPs in the region with a pairwise r(2) >or= 0.90 or 100% of SNPs with a pairwise r(2) >or= 0.80. Genotyping of polymorphisms was performed by using the Affymetrix MegAllele Targeted Genotyping System. A logistic regression model was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).
Of 7 tag SNPs that were assessed, 2 polymorphisms in the 3' flanking region of the PGR gene, reference SNP identification number (rs) 11224561 (rs11224561) and rs471767, were associated with the risk of endometrial cancer. The cytosine/cytosine (CC) genotype of SNP rs11224561 was associated with decreased risk (OR, 0.68; 95% CI, 0.50-0.92) compared with the thymine/thymine (TT) genotype. Carrying the guanine (G) allele of the rs471767 SNP also was associated with decreased risk, although the association was not statistically significant (OR, 0.78, 95%CI, 0.59-1.04 and OR, 0.32, 95%CI, 0.03-3.05 for the adenine [A]G and GG genotypes, respectively, compared with the homozygote AA).
The current findings suggested that polymorphisms in the 3' flanking region of the PGR gene may be associated with the risk of endometrial cancer.
孕激素受体（PGR）基因中的单核苷酸多态性（SNP）与子宫内膜癌风险相关。然而，据作者所知，迄今为止尚无研究系统评估PGR基因在子宫内膜癌发生中的作用。
本研究使用了在上海子宫内膜癌研究中收集的暴露信息和DNA样本，该研究是一项基于人群的病例对照研究，包括1204例新发病例和1212例年龄及频率匹配的人群对照。利用国际人类基因组单体型图计划（HapMap计划）中的汉族数据，为PGR基因及其5千碱基（kb）侧翼区域确定了7个标签SNP，其成对相关系数（r²）≥0.90。这7个SNP捕获了该区域中r²≥0.90的SNP的92%，或r²≥0.80的SNP的100%。多态性基因分型采用Affymetrix MegAllele靶向基因分型系统进行。采用逻辑回归模型计算调整后的比值比（OR）和95%置信区间（95%CI）。
在评估的7个标签SNP中，PGR基因3'侧翼区域的2个多态性，即参考SNP识别号（rs）11224561（rs11224561）和rs471767，与子宫内膜癌风险相关。与胸腺嘧啶/胸腺嘧啶（TT）基因型相比，SNP rs11224561的胞嘧啶/胞嘧啶（CC）基因型与风险降低相关（OR，0.68；95%CI，0.5-0.9）。携带rs471767 SNP的鸟嘌呤（G）等位基因也与风险降低相关，尽管该关联无统计学意义（与纯合子AA相比，腺嘌呤[A]G和GG基因型的OR分别为0.78，95%CI，0.59-1.04和OR，0.32，95%CI，0.03-3.05）。
目前的研究结果表明，PGR基因3'侧翼区域的多态性可能与子宫内膜癌风险相关。
