TY - JOUR
TI - Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers
AU - Neasham, D.
AU - Gallo, V.
AU - Guarrera, S.
AU - Dunning, A.
AU - Overvad, K.
AU - Tjonneland, A.
AU - Clavel-Chapelon, F.
AU - Linseisen, J.P.
AU - Malaveille, C.
AU - Ferrari, P.
AU - Boeing, H.
AU - Benetou, V.
AU - Trichopoulou, A.
AU - Palli, D.
AU - Crosignani, P.
AU - Tumino, R.
AU - Panico, S.
AU - Bueno-De-Mesquita, H.B.
AU - Peeters, P.H.
AU - van Gib, C.H.
AU - Lund, E.
AU - Gonzalez, C.A.
AU - Martinez, C.
AU - Dorronsoro, M.
AU - Barricarte, A.
AU - Navarro, C.
AU - Quiros, J.R.
AU - Berglund, G.
AU - Jarvholm, B.
AU - Khaw, K.T.
AU - Key, T.J.
AU - Bingham, S.
AU - Diaz, T.M.J.
AU - Riboli, E.
AU - Matullo, G.
AU - Vineis, P.
JO - DNA Repair
PY - 2009
VL - 8
TODO - 1
SP - 60-71
PB - 
SN - 1568-7864
TODO - 10.1016/j.dnarep.2008.08.012
TODO - 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
TODO - 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.
ER -