UGT1A1 genetic polymorphisms, endogenous estrogen exposure, soy food intake, and endometrial cancer risk
UGT1A1 genetic polymorphisms, endogenous estrogen exposure, soy food intake, and endometrial cancer risk
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DOI：
10.1158/1055-9965.epi-07-0752
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发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Shu, Xiao-Ou
中科院分区：
文献类型：
--
作者：
Deming, Sandra L.;Zheng, Wei;Shu, Xiao-Ou
雌激素暴露在子宫内膜癌的发展中起着至关重要的作用。雌激素代谢UGT 1A 1基因的遗传变异可能改变雌激素暴露对子宫内膜癌风险的影响我们在一项基于人群的病例对照研究中对这一假设进行了检验，该研究包括1,047例子宫内膜癌病例和1,035例对照，这些病例和对照完成了面对面访谈，并对UGT 1A 1多态性rs 2070959（A/G）、rs 887829（G/A）和rs 8175347（6/7 TA重复）进行了基因分型。评估的雌激素缺乏相关因素包括月经特征、口服避孕药的使用、体重指数、腰臀比和豆制品摄入量。条件Logistic回归用于计算比值比和95%置信区间。rs 207 O 959多态性的纯合子变异基因型（G/G）与子宫内膜癌风险降低显著相关（比值比，0.5; 95%置信区间，0.3-0.8）。子宫内膜癌风险与rs 887829和rs 8175347多态性基因型之间没有显著相关性。基因型和雌激素暴露标志物的联合效应分析发现，在具有rs 207 O 959多态性的纯合变异基因型和绝经后、低体重指数和低大豆食物摄入的人中，子宫内膜癌的风险最低，尽管乘法相互作用的检验不显著。综上所述，这些数据表明，G/G基因型（rs 207 O 959）在UGT 1A 1基因可能会降低子宫内膜癌的风险，这种效果是最明显的妇女与低水平的内源性雌激素暴露或低大豆食品摄入量。
Estrogen exposures play a critical role in the development of endometrial cancer. Genetic variation in the estrogen metabolism UGT1A1 gene may modify the effect of estrogenic exposures on endometrial cancer risk. We tested this hypothesis in a population-based case-control study of 1,047 endometrial cancer cases and 1,035 controls who completed an in-person interview and were genotyped for the UGT1A1 polymorphisms rs2070959 (A/G), rs887829 (G/A), and rs8175347 (6/7 TA repeats). Estrogen exposure-related factors evaluated include menstrual characteristics, oral contraceptive use, body mass index, waist-hip ratio, and soy food intake. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. The homozygote variant genotype (G/G) of the rs207O959 polymorphism was significantly associated with a reduced risk of endometrial cancer (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). No significant associations between endometrial cancer risk and genotype were seen for the rs887829 and rs8175347 polymorphisms. Analysis of the joint effects of genotype and markers of estrogen exposure found the lowest risk of endometrial cancer among those with the homozygous variant genotype of the rs207O959 polymorphism and who were postmenopausal, had low body mass index, and had low soy food intake, although a test for multiplicative interaction was not significant. Taken together, these data suggest that the G/G genotype (rs207O959) in the UGT1A1 gene may decrease the risk of endometrial cancer and that this effect is most evident among women with low levels of endogenous estrogen exposure or with low soy food intake.