Polymorphisms in the DNA repair gene XPD: Correlations with risk and age at onset of basal cell carcinoma

The XPD protein has a dual function, both in nucleotide excision repair and in basal transcription. We have studied the role of two nucleotide substit utions in the XPD gene, one in exon 23 leading to an amino acid substitutio n (Lys751Gln) and one silent in exon 6 in relation to basal cell carcinoma (BCC), Both are twoallele polymorphisms, with the nucleobases A and C at th e given positions. We genotyped psoriasis patients with and without BCC and nonpsoriatic persons with and without BCC (4 x 20 persons). The choice to study psoriasis patients was motivated by their high genotoxic exposure via treatment and their high relative rate of early BCC, Subjects carrying two A alleles (AA genotype) in exon 23 were at 4.3-fold higher risk of BCC tha n subjects with two C alleles (95% CI, 0.79-23.57). In addition, the mean a ge at first skin tumor for BCC cases with the AA genotype was significantly lower than the mean age for BCC cases with the AC or CC genotype (P = 0.01 2). Thus, the variant C-allele of exon 23 may be protective. The exon 6 gen otype was associated with the risk of BCC among the psoriasis patients; pso riatics carrying two A alleles in exon 6 were at 5.3-fold higher risk of BC C than psoriatics with two C alleles (95% CI, 0.78-36.31). For the psoriati cs, the mean age at onset of BCC for cases with the AA genotype was margina lly lower than the mean age for cases with genotype AC or CC (P = 0.060), O ur results raise the possibility that the polymorphisms in the XPD gene may be contributing factors in the risk of BCC development. They are, therefor e, important candidates for future studies in susceptibility to cancer.