Year: 2011
Type: article
Study design: Observational Study
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Certain ERCC5, LIG1, XPA, and XPC genotypes might influence endometrial cancer risk. IMPACT: 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.
Institutions: University of Washington, Fred Hutch Cancer Center
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1355612696, Mentoring and Research in Cancer Epidemiology , G251835456, G292018060, BREAST CANCER AND THE BIRTH CONTROL PILL, ENDOMETRIAL CANCER AND CYP1A1, GSTM1 AND POLYMORPHISMS, G5304219631, G5650272604, Epidemiology of Ovarian Cancer:New Hypotheses, G671768105, Molecular Epidemiology of Endometrial Cancer, ENDOMETRIAL CANCER AND POSTMENOPAUSAL HORMONE THERAPY, RESEARCH IN CANCER EPIDEMIOLOGY, G988737349
OpenAlex ID: W2145467303