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.
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 ERCC5rs4150386 C, LIG1rs3730865 C, XPArs2808667 T, or XPCrs3731127 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.
Authors: Jennifer A Doherty; Noel S Weiss; Robert J Freeman; Douglas A Dightman; Perry J Thornton; John R Houck; Lynda F Voigt; Mary Anne Rossing; Stephen M Schwartz; Chu Chen Journal: Cancer Epidemiol Biomarkers Prev Date: 2005-02 Impact factor: 4.254
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Authors: Veronica Wendy Setiawan; Fredrick Schumacher; Jennifer Prescott; Jeffrey Haessler; Jennifer Malinowski; Nicolas Wentzensen; Hannah Yang; Stephen Chanock; Louise Brinton; Patricia Hartge; Jolanta Lissowska; S Lani Park; Iona Cheng; William S Bush; Dana C Crawford; Giske Ursin; Pamela Horn-Ross; Leslie Bernstein; Lingeng Lu; Harvey Risch; Herbert Yu; Lori C Sakoda; Jennifer Doherty; Chu Chen; Rebecca Jackson; Shagufta Yasmeen; Michele Cote; Jonathan M Kocarnik; Ulrike Peters; Peter Kraft; Immaculata De Vivo; Christopher A Haiman; Charles Kooperberg; Loic Le Marchand Journal: Carcinogenesis Date: 2014-05-15 Impact factor: 4.741