This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matullo, G. Articles by Palli, D. Search for Related Content PubMed PubMed Citation Articles by Matullo, G. Articles by Palli, D.

Combination of DNA Repair Gene Single Nucleotide Polymorphisms and Increased Levels of DNA Adducts in a Population-based Study¹

Dipartimento di Genetica, Biologia e Biochimica, Università di Torino [G. Mat., S. G.] and Unità di Epidemiologia dei Tumori, Dipartimento di Scienze Biomediche e Oncologia Umana [S. Po., P. V.], 10126, Torino; I. S. I Foundation, Institute for Scientific Interchange, Villa Gualino, 10133, Torino [G. Mat., P. V.]; Unità di Epidemiologia, Istituto Nazionale Tumori, 20100, Milano [V. K., F. B.]; Unità di Epidemiologia Molecolare e Nutrizionale, [G. Mas., D. P.] and Laboratorio di Biologia Molecolare [M. P., A. M.], Centro per lo Studio e La Prevenzione Oncologica, 10133, Firenze; Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Napoli [S. Pa.]; and Registro Tumori–Azienda Ospedaliera "Civile–M.P. Arezzo," 97100, Ragusa [R. T.], Italy

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.

This article has been cited by other articles:

				J. Lin, G. E. Swan, P. G. Shields, N. L. Benowitz, J. Gu, C. I. Amos, M. de Andrade, M. R. Spitz, and X. Wu Mutagen Sensitivity and Genetic Variants in Nucleotide Excision Repair Pathway: Genotype-Phenotype Correlation Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2065 - 2071. [Abstract] [Full Text] [PDF]

				P. Vineis, S. Anttila, S. Benhamou, M. Spinola, A. Hirvonen, C. Kiyohara, S. J. Garte, R. Puntoni, A. Rannug, R. C. Strange, et al. Evidence of gene gene interactions in lung carcinogenesis in a large pooled analysis Carcinogenesis, September 1, 2007; 28(9): 1902 - 1905. [Abstract] [Full Text] [PDF]

				P Vineis, F Veglia, S Garte, C Malaveille, G Matullo, A Dunning, M Peluso, L Airoldi, K Overvad, O Raaschou-Nielsen, et al. Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers Ann. Onc., July 1, 2007; 18(7): 1230 - 1242. [Abstract] [Full Text] [PDF]

				M. Manuguerra, F. Saletta, M. R. Karagas, M. Berwick, F. Veglia, P. Vineis, and G. Matullo XRCC3 and XPD/ERCC2 Single Nucleotide Polymorphisms and the Risk of Cancer: A HuGE Review Am. J. Epidemiol., August 15, 2006; 164(4): 297 - 302. [Abstract] [Full Text] [PDF]

				H. B. Ketelslegers, R. W.H. Gottschalk, R. W.L. Godschalk, A. M. Knaapen, F. J. van Schooten, R. F.M.H. Vlietinck, J. C.S. Kleinjans, and J. H.M. van Delft Interindividual variations in DNA adduct levels assessed by analysis of multiple genetic polymorphisms in smokers. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 624 - 629. [Abstract] [Full Text] [PDF]

				R. C. Millikan, A. Hummer, C. Begg, J. Player, A. R. de Cotret, S. Winkel, H. Mohrenweiser, N. Thomas, B. Armstrong, A. Kricker, et al. Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study Carcinogenesis, March 1, 2006; 27(3): 610 - 618. [Abstract] [Full Text] [PDF]

				S. A.S. Langie, A. M. Knaapen, K. J.J. Brauers, D. van Berlo, F.-J. van Schooten, and R. W.L. Godschalk Development and validation of a modified comet assay to phenotypically assess nucleotide excision repair Mutagenesis, March 1, 2006; 21(2): 153 - 158. [Abstract] [Full Text] [PDF]

				J. Bigler, C. M. Ulrich, T. Kawashima, J. Whitton, and J. D. Potter DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2501 - 2508. [Abstract] [Full Text] [PDF]

				M. Majumder, N. Sikdar, R. R. Paul, and B. Roy Increased Risk of Oral Leukoplakia and Cancer Among Mixed Tobacco Users Carrying XRCC1 Variant Haplotypes and Cancer Among Smokers Carrying Two Risk Genotypes: One on Each of Two Loci, GSTM3 and XRCC1 (Codon 280) Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2106 - 2112. [Abstract] [Full Text] [PDF]

				M. Peluso, A. Munnia, G. Hoek, M. Krzyzanowski, F. Veglia, L. Airoldi, H. Autrup, A. Dunning, S. Garte, P. Hainaut, et al. DNA Adducts and Lung Cancer Risk: A Prospective Study Cancer Res., September 1, 2005; 65(17): 8042 - 8048. [Abstract] [Full Text] [PDF]

				J. Shen, M. D. Gammon, M. B. Terry, L. Wang, Q. Wang, F. Zhang, S. L. Teitelbaum, S. M. Eng, S. K. Sagiv, M. M. Gaudet, et al. Polymorphisms in XRCC1 Modify the Association between Polycyclic Aromatic Hydrocarbon-DNA Adducts, Cigarette Smoking, Dietary Antioxidants, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 336 - 342. [Abstract] [Full Text] [PDF]

				S. Benhamou and A. Sarasin ERCC2 /XPD Gene Polymorphisms and Lung Cancer: A HuGE Review Am. J. Epidemiol., January 1, 2005; 161(1): 1 - 14. [Abstract] [Full Text] [PDF]

				D. Butkiewicz, O. Popanda, A. Risch, L. Edler, H. Dienemann, V. Schulz, K. Kayser, P. Drings, H. Bartsch, and P. Schmezer Association between the Risk for Lung Adenocarcinoma and a (-4) G-to-A Polymorphism in the XPA Gene Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2242 - 2246. [Abstract] [Full Text] [PDF]

				M. Peluso, M. Neri, G. Margarino, C. Mereu, A. Munnia, M. Ceppi, M. Buratti, R. Felletti, F. Stea, R. Quaglia, et al. Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms Carcinogenesis, December 1, 2004; 25(12): 2459 - 2465. [Abstract] [Full Text] [PDF]

				O. Popanda, T. Schattenberg, C. T. Phong, D. Butkiewicz, A. Risch, L. Edler, K. Kayser, H. Dienemann, V. Schulz, P. Drings, et al. Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer Carcinogenesis, December 1, 2004; 25(12): 2433 - 2441. [Abstract] [Full Text] [PDF]