U. Vogel et al., Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited, CARCINOGENE, 22(6), 2001, pp. 899-904
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.