Weiss Jocelyn M, Weiss Noel S, Ulrich Cornelia M, Doherty Jennifer A, Chen Chu
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
Gynecol Oncol. 2006 Dec;103(3):891-6. doi: 10.1016/j.ygyno.2006.05.020. Epub 2006 Jun 23.
Certain nucleotide excision repair (NER) genotypes appear to be associated with an altered risk of endometrial cancer. These associations could be modified by characteristics and exposures that themselves influence risk of disease.
We conducted a population-based case-control study in western Washington State to address the role of specific NER genotypes in conjunction with relevant exposures, such as postmenopausal hormone therapy, obesity, parity, oral contraceptive use, and cigarette smoking on risk of endometrial cancer. Case women (n=371), ages 50-69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n=420), matched to cases on age and county of residence, were selected using random-digit dialing (ages 50-65) and random selection from HCFA data files (ages 66-69).
Risk of endometrial cancer was not associated with ERCC1, ERCC2 (XPD), ERCC4 (XPF), or ERCC5 (XPG) genotype. A reduced risk of endometrial cancer was observed with presence of the XPA g23a variant allele, but only among women with a history of oral contraceptive use (OR 0.47, 95% CI 0.32-0.69). A decreased risk associated with carriage of at least one variant allele for both XPC A499V and XPC K939Q was restricted to women with BMI<30 kg/m2 (OR 0.45, 95% CI 0.25-0.82). The size of the association between these genotypes and risk of endometrial cancer did not differ by postmenopausal hormone use, parity, or smoking.
Our study provides limited evidence for interactions between NER genotypes and DNA damage-causing exposures in the etiology of endometrial cancer. Subsequent studies are needed to confirm the observed associations.
某些核苷酸切除修复（NER）基因型似乎与子宫内膜癌风险改变有关。这些关联可能会受到自身影响疾病风险的特征和暴露因素的修饰。
我们在华盛顿州西部开展了一项基于人群的病例对照研究，以探讨特定NER基因型与相关暴露因素（如绝经后激素治疗、肥胖、生育状况、口服避孕药使用和吸烟）对子宫内膜癌风险的联合作用。病例组女性（n = 371）年龄在50 - 69岁之间，于1994年至1999年期间被诊断为浸润性子宫内膜癌。对照组女性（n = 420），根据年龄和居住县与病例组匹配，通过随机数字拨号法选取年龄在50 - 65岁的女性，并从医疗保险和医疗补助服务中心（HCFA）数据文件中随机选取年龄在66 - 69岁的女性。
子宫内膜癌风险与ERCC1、ERCC2（XPD）、ERCC4（XPF）或ERCC5（XPG）基因型无关。在携带XPA g23a变异等位基因的女性中观察到子宫内膜癌风险降低，但仅在有口服避孕药使用史的女性中出现（比值比0.47，95%可信区间0.32 - 0.69）。与同时携带XPC A499V和XPC K939Q至少一个变异等位基因相关的风险降低仅限于体重指数（BMI）<30 kg/m²的女性（比值比0.45，95%可信区间0.25 - 0.82）。这些基因型与子宫内膜癌风险之间关联的大小在绝经后激素使用、生育状况或吸烟方面并无差异。
我们的研究为NER基因型与导致DNA损伤的暴露因素在子宫内膜癌病因学中的相互作用提供了有限的证据。后续研究需要证实所观察到的关联。
