title: Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers.
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.
authors.affiliation: Division of Epidemiology, Public Health & Primary Care, Imperial College, UK. david.neasham@googlemail.com
authors.forename: David
authors.initials: D
authors.lastname: Neasham
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.forename: Alison
authors.initials: A
authors.lastname: Dunning
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Francoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Linseisen
authors.forename: Christian
authors.initials: C
authors.lastname: Malaveille
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Paolo
authors.initials: P
authors.lastname: Crosignani
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-De-Mesquita
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gib
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonzalez
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Josè R
authors.initials: JR
authors.lastname: Quiros
authors.forename: Goran
authors.initials: G
authors.lastname: Berglund
authors.forename: Bengt
authors.initials: B
authors.lastname: Jarvholm
authors.forename: Kay Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Tormo M Jose
authors.initials: TM
authors.lastname: Diaz
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D015331:Cohort Studies; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D009026:Mortality; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors