Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers

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 analyz...

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Published in:DNA repair Vol. 8; no. 1; pp. 60 - 71
Main Authors: Neasham, David, Gallo, Valentina, Guarrera, Simonetta, Dunning, Alison, Overvad, Kim, Tjonneland, Anne, Clavel-Chapelon, Francoise, Linseisen, Jakob P., Malaveille, Christian, Ferrari, Pietro, 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
Format: Journal Article
Language:English
Published: Amsterdam Elsevier B.V 2009
Elsevier
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Summary: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.
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ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2008.08.012