Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited

The XPD gene product has a dual function in basal transcription and in nucl eotide excision repair. We have previously reported that two polymorphisms in the gene, one silent mutation in codon 156 of exon 6 and one giving rise to a Lys --> Gln substitution in codon 751 of exon 23, showed signs of bei ng associated with basal cell carcinoma in a Scandinavian study group of ps oriasis patients and non-psoriatics with and without basal cell carcinoma [ Dybdahl, Vogel, Frentz, Wallin and Nexo (1999) Cancer Epidemiol. Biomark. P rev., 8, 77-81], In both polymorphisms, the CC genotype appeared to be prot ective against basal cell carcinoma. Here, we have genotyped an American st udy group of basal cell carcinoma patients and controls without skin cancer for the two polymorphisms, In addition, we studied an A -->G polymorphism in codon 312 of exon 10, which results in an Asp --> Asn substitution in a conserved region of XPD, In the whole study group, subjects carrying the AA and AC genotype in exon 6 were at 1.9-fold higher risk of basal cell carci noma (P = 0.062, CI 0.96-3.75). If only subjects without a family history o f non-melanoma skin cancer were included, subjects carrying AA or AC genoty pe were at 3.3-fold higher risk of basal cell carcinoma (P = 0.007, CI 1.35 -8.18). Among subjects with a family history of non-melanoma skin cancer, s ubjects with an AG or AA genotype in codon 312 of exon 10 were at 5.25-fold increased risk of basal cell carcinoma (P = 0.027, CI 1.15-23.93). A prote ctive effect of the CC genotype in exon 23 could not be confirmed, Cases wi th a family history of skin cancer had statistically significantly differen t allele frequencies of the polymorphisms in exon 6 and exon 10 from cases without family history of non-melanoma skin cancer, Our results indicate th at the exon 6(A) allele is a risk factor in basal cell carcinoma.