Περίληψη:
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. © 2008 Elsevier B.V. All rights reserved.
Συγγραφείς:
Neasham, D.
Gallo, V.
Guarrera, S.
Dunning, A.
Overvad, K.
Tjonneland, A.
Clavel-Chapelon, F.
Linseisen, J.P.
Malaveille, C.
Ferrari, P.
Boeing, H.
Benetou, V.
Trichopoulou, A.
Palli, D.
Crosignani, P.
Tumino, R.
Panico, S.
Bueno-De-Mesquita, H.B.
Peeters, P.H.
van Gib, C.H.
Lund, E.
Gonzalez, C.A.
Martinez, C.
Dorronsoro, M.
Barricarte, A.
Navarro, C.
Quiros, J.R.
Berglund, G.
Jarvholm, B.
Khaw, K.T.
Key, T.J.
Bingham, S.
Diaz, T.M.J.
Riboli, E.
Matullo, G.
Vineis, P.
Λέξεις-κλειδιά:
adult; aged; allelism; article; cancer incidence; cancer mortality; cohort analysis; DNA repair; DNA strand breakage; excision repair; female; genetic association; genetic polymorphism; genetic risk; genetic variability; genotype; human; human tissue; major clinical study; male; priority journal; prospective study; risk assessment, Cohort Studies; DNA Breaks, Double-Stranded; DNA Repair; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Mortality; Neoplasms; Polymorphism, Genetic; Prospective Studies; Risk Factors
