Nucleotide excision repair genotype and the incidence of endometrial cancer: effect of other risk factors on the association.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Weiss
Jocelyn M
JM
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. weissjoc@mail.nih.gov
Weiss
Noel S
NS
Ulrich
Cornelia M
CM
Doherty
Jennifer A
JA
Chen
Chu
C
D000368:Aged; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012307:Risk Factors; D014861:Washington / Q000453:epidemiology; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human