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

Research output: Contribution to journalArticle

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 call influence mortality. (C) 2008 Elsevier B.V. All rights reserved.

Details

Authors
  • David Neasham
  • Valentina Gallo
  • Simonetta Guarrera
  • Alison Dunning
  • Kim Overvad
  • Anne Tjonneland
  • Francoise Clavel-Chapelon
  • Jakob P. Linseisen
  • Christian Malaveille
  • Pietro Ferrari
  • Heiner Boeing
  • Vassiliki Benetou
  • Antonia Trichopoulou
  • Domenico Palli
  • Paolo Crosignani
  • Rosario Tumino
  • Salvatore Panico
  • H. Bas Bueno-De-Mesquita
  • Petra H. Peeters
  • Carla H. van Gib
  • And 16 others
  • Eiliv Lund
  • Carlos A. Gonzalez
  • Carmen Martinez
  • Miren Dorronsoro
  • Aurelio Barricarte
  • Carmen Navarro
  • Jose R. Quiros
  • Göran Berglund
  • Bengt Jarvholm
  • Kay Tee Khaw
  • Timothy J. Key
  • Sheila Bingham
  • Tormo M. Jose Diaz
  • Elio Riboli
  • Giuseppe Matullo
  • Paolo Vineis
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine

Keywords

  • Mortality, DNA repair, Prospective study, Cancer
Original languageEnglish
Pages (from-to)60-71
JournalDNA Repair
Volume8
Issue number1
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes