Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study

Giuseppe Matullo, Marco Peluso, Silvia Polidoro, Simonetta Guarrera, Armelle Munnia, Vittorio Krogh, Giovanna Masala, Franco Berrino, Salvatore Panico, Rosario Tumino, Paolo Vineis, Domenico Palli

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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 109 nucleotides by 32P-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.

Original languageEnglish
Pages (from-to)674-677
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume12
Issue number7
Publication statusPublished - Jul 1 2003

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Matullo, G., Peluso, M., Polidoro, S., Guarrera, S., Munnia, A., Krogh, V., Masala, G., Berrino, F., Panico, S., Tumino, R., Vineis, P., & Palli, D. (2003). Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study. Cancer Epidemiology Biomarkers and Prevention, 12(7), 674-677.