Neasham, David; Gallo, Valentina; Guarrera, Simonetta; Dunning, Alison; Overvad, Kim; Tjonneland, Anne; Clavel-Chapelon, Francoise; Linseisen, Jakob P; Malaveille, Christian; Ferrari, Pietro; +26 more... Boeing, Heiner; Benetou, Vassiliki; Trichopoulou, Antonia; Palli, Domenico; Crosignani, Paolo; Tumino, Rosario; Panico, Salvatore; Bueno-De-Mesquita, H Bas; Peeters, Petra H; van Gib, Carla H; Lund, Eiliv; Gonzalez, Carlos A; Martinez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Navarro, Carmen; Quiros, Josè R; Berglund, Goran; Jarvholm, Bengt; Khaw, Kay Tee; Key, Timothy J; Bingham, Sheila; Diaz, Tormo M Jose; Riboli, Elio; Matullo, Giuseppe; Vineis, Paolo; (2009) Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers. DNA repair, 8 (1). pp. 60-71. ISSN 1568-7864 DOI: https://doi.org/10.1016/j.dnarep.2008.08.012
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Abstract
We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.
| Item Type | Article |
|---|---|
| Keywords | Cohort Studies, *DNA Breaks, Double-Stranded, DNA Repair/*genetics, Genetic Predisposition to Disease, Genotype, Humans, Incidence, *Mortality, Neoplasms/*epidemiology/*genetics, *Polymorphism, Genetic, Prospective Studies, Risk Factors, Cohort Studies, DNA Breaks, Double-Stranded, DNA Repair, genetics, Genetic Predisposition to Disease, Genotype, Humans, Incidence, Mortality, Neoplasms, epidemiology, genetics, Polymorphism, Genetic, Prospective Studies, Risk Factors |
| Faculty and Department | Faculty of Public Health and Policy > Public Health, Environments and Society |
| Research Centre | Centre for Global Non-Communicable Diseases (NCDs) |
| PubMed ID | 18824251 |
| ISI | 262057500008 |
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