title: Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study.
abstract: Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. We investigated the role of SNPs in three DNA repair genes (X-ray repair cross-complementing group 1-Arg399Gln, exon 10; X-ray repair cross-complementing group 3-Thr241Met, exon 7; and xeroderma pigmentosum-D-Lys751Gln, exon 23) and their combination, in modulating the levels of "bulky" DNA adducts in a population sample of 628 Italian healthy individuals belonging to the prospective European project "European Prospective Investigation into Cancer and Nutrition." DNA-adduct levels were measured as relative adduct level per 10(9) nucleotides by (32)P-post DNA labeling assay in WBCs from peripheral blood. Genotyping was performed by PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. We found a dose-response relationship between the number of at-risk alleles and levels of adducts (P = 0.0046). Individuals with at least three variant alleles had a statistically significant odds ratio (OR) for being in the highest tertile of adducts compared with those with undetectable adducts [three alleles, adjusted OR = 5.07, 95% confidence interval (CI) = 1.29-19.9; four alleles, adjusted OR = 5.03, 95% CI = 1.18-21.45; five alleles, adjusted OR = 7.65, 95% CI = 0.94-62.2]. Our study suggests that the combined effect of multiple variant alleles may be more important than the investigation of single SNP in modulating DNA repair capacity.
authors.affiliation: Dipartimento di Genetica, Biologia e Biochimica, Università di Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Marco
authors.initials: M
authors.lastname: Peluso
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.forename: Armelle
authors.initials: A
authors.lastname: Munnia
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D018736:DNA Adducts / Q000097:blood / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007962:Leukocytes / Q000378:metabolism; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D014983:Xeroderma Pigmentosum / Q000235:genetics
chemical_list: D018736:DNA Adducts