Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer.
Exposure to estrogens is a likely cause of endometrial cancer, but the means by which estrogens exert this effect are not entirely clear. One hypothesis is that certain estrogen metabolites bind to the DNA, forming bulky adducts that damage the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such damage may increase her risk of endometrial cancer. We conducted a population-based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer. Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420) were selected using random-digit dialing (ages 50-65 years) and by random selection from Health Care Financing Administration data files (ages 66-69 years). Genotyping assays were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a), ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer.
Weiss
Jocelyn M
JM
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational and Environmental Epidemiology Branch, 6120 Executive Boulevard, EPS 8123, MSC 7240, Rockville, MD 20852, USA. weissjoc@mail.nih.gov
Weiss
Noel S
NS
Ulrich
Cornelia M
CM
Doherty
Jennifer A
JA
Voigt
Lynda F
LF
Chen
Chu
C
D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D018736:DNA Adducts; D004268:DNA-Binding Proteins