title: A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism.
abstract: We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion of 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 that the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Johns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from the Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unselected donors from NIH. We also found a single nucleotide polymorphism in exon 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restriction 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 the PAT locus. We developed an allele-specific complementation assay utilizing post-UV host cell reactivation to assess DNA repair capacity of polymorphic 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 molecular epidemiological studies of cancer susceptibility.
authors.affiliation: National Cancer Institute, National Institute of Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Khan
authors.forename: E J
authors.initials: EJ
authors.lastname: Metter
authors.forename: R E
authors.initials: RE
authors.lastname: Tarone
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
authors.forename: L
authors.initials: L
authors.lastname: Grossman
authors.forename: M
authors.initials: M
authors.lastname: Hedayati
authors.forename: S J
authors.initials: SJ
authors.lastname: Bale
authors.forename: S
authors.initials: S
authors.lastname: Emmert
authors.forename: K H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005816:Genetic Complementation Test; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011061:Poly A / Q000235:genetics*; D011071:Poly T / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D011061:Poly A; D011071:Poly T; C008950:poly A-T