Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Sep;20(9):1873-82. doi: 10.1158/1055-9965.EPI-11-0119. Epub 2011 Jul 12.
Exposure to estrogens increases the risk of endometrial cancer. Certain estrogen metabolites can form bulky DNA adducts, which are removed via nucleotide excision repair (NER), and the ability to carry out this repair might be related to endometrial cancer risk.
We examined 64 tag and functional single-nucleotide polymorphisms (SNPs) in the NER genes ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC4 (XPF), ERCC5 (XPG), LIG1, XPA, and XPC in a population-based case-control study in Washington state, with 783 endometrial cancer cases and 795 controls.
The presence of ERCC5 rs4150386 C, LIG1 rs3730865 C, XPA rs2808667 T, or XPC rs3731127 T alleles was associated with risk of endometrial cancer, with respective age-, county-, and reference year-adjusted per-allele ORs and 95% CIs of 0.68 (0.53-0.87, P = 0.002), 1.46 (1.02-2.10, P = 0.04), 0.71 (0.52-0.97, P = 0.03), and 1.57 (1.13-2.17, P = 0.007), respectively.
Certain ERCC5, LIG1, XPA, and XPC genotypes might influence endometrial cancer risk.
Because of multiple redundancies in DNA repair pathways (and therefore a low prior probability) and the large number of associations examined, false-positive findings are likely. Further characterization of the relation between variation in NER genes and endometrial cancer risk is warranted.
暴露于雌激素会增加子宫内膜癌的风险。某些雌激素代谢物可以形成大块的 DNA 加合物，这些加合物通过核苷酸切除修复 (NER) 被清除，而进行这种修复的能力可能与子宫内膜癌的风险有关。
我们在华盛顿州进行了一项基于人群的病例对照研究，共纳入了 783 例子宫内膜癌病例和 795 例对照，检测了 NER 基因 ERCC1、ERCC2 (XPD)、ERCC3 (XPB)、ERCC4 (XPF)、ERCC5 (XPG)、LIG1、XPA 和 XPC 中的 64 个标签和功能单核苷酸多态性 (SNP)。
携带 ERCC5 rs4150386 C、LIG1 rs3730865 C、XPA rs2808667 T 或 XPC rs3731127 T 等位基因与子宫内膜癌的发病风险相关，相应的年龄、县和参考年份调整后的每个等位基因的比值比 (OR) 及其 95%置信区间 (CI) 分别为 0.68(0.53-0.87，P=0.002)、1.46(1.02-2.10，P=0.04)、0.71(0.52-0.97，P=0.03)和 1.57(1.13-2.17，P=0.007)。
某些 ERCC5、LIG1、XPA 和 XPC 基因型可能影响子宫内膜癌的风险。
由于 DNA 修复途径的多重冗余（因此先验概率较低）和大量被检查的关联，假阳性发现很可能存在。进一步研究 NER 基因变异与子宫内膜癌风险之间的关系是有必要的。
