Influence of XPD variant alleles on p53 mutations in lung tumors of nonsmokers and smokers

摘要

The DNA repair protein XPD is involved in the transcription-coupled nucleotide excision repair of DNA lesions induced by many tobacco and environmental carcinogens, Common polymorphisms in XPD exon 10 (G > A, Asp312Asn) and exon 23 (A > C, Lys751 Gin) have been identified, and lung cancer cases homozygous for the variant allele in either exon have been reported to have a reduced repair capacity against benzo[alpha]pyrene-induced DNA damage, We therefore investigated a possible effect of these variant alleles on the p53 mutation frequency and spectrum among 97 Swedish lung cancer patients. Transversions were found to occur more frequently among patients with at least one variant allele than among wild type homozygotes. The XPD variant alleles may thus be associated with reduced DNA repair proficiency. This finding is not in accord with the previous report that associated the exon 23 wild type allele with increased frequency of X-ray-induced chromatid aberrations