Genetic variation in XRCC1, sun exposure, and risk of skin cancer.
The XRCC1 gene is involved in the base excision repair pathway. We assessed the associations of polymorphisms and haplotypes in XRCC1 with skin cancer risk in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma (SCC) and 300 basal cell carcinoma (BCC), and 873 controls). We genotyped four haplotype-tagging single-nucleotide polymorphisms (Arg194Trp, C26602T, Arg399Gln, and Gln632Gln). There was no significant difference in frequency distribution between cases and controls for any of the five inferred common haplotypes. We observed that the 399Gln allele was inversely associated with SCC risk. This inverse association was only seen among those who had five or more lifetime sunburns, those with a family history of skin cancer, and those in the highest tertile of cumulative sun exposure in a bathing suit, but not among those with low risk defined by these risk factors. We also observed a significant association of the carriage of 194Trp allele with increased SCC risk, which was modified by family history of skin cancer. These two polymorphisms were not associated with BCC or melanoma risk. Our data suggest that the Arg194Trp and Arg399Gln polymorphisms may be differently associated with skin cancer risk according to exposure dose and skin cancer type.
Han
J
J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA. jiali.han@channing.harvard.edu
Hankinson
S E
SE
Colditz
G A
GA
Hunter
D J
DJ
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013471:Sunburn / Q000150:complications*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human