A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism

We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion o f 83 bases of A and T [poly(AT)] and a 5 base deletion within intron 9, We developed a PCR assay to resolve the XPC PAT+ and PAT- alleles and found th at the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Jo hns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from th e Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unsele cted donors from NIH, We also found a single nucleotide polymorphism in exo n 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restr iction site. This XPC exon 15 single nucleotide polymorphism occurred at a frequency of 0.38 in 98 NIH donors and is in linkage disequilibrium with th e PAT locus. We developed an allele-specific complementation assay utilizin g post-UV host cell reactivation to assess DNA repair capacity of polymorph ic alleles, We found similar DNA repair with XPC 2920A and XPC 2920C, These common polymorphisms in the XPC DNA repair gene may be useful for molecula r epidemiological studies of cancer susceptibility.