title: Low integrated DNA repair score and lung cancer risk.
abstract: DNA repair is a prime mechanism for preventing DNA damage, mutation, and cancers. Adopting a functional approach, we examined the association with lung cancer risk of an integrated DNA repair score, measured by a panel of three enzymatic DNA repair activities in peripheral blood mononuclear cells. The panel included assays for AP endonuclease 1 (APE1), 8-oxoguanine DNA glycosylase (OGG1), and methylpurine DNA glycosylase (MPG), all of which repair oxidative DNA damage as part of the base excision repair pathways. A blinded population-based case-control study was conducted with 96 patients with lung cancer and 96 control subjects matched by gender, age (±1 year), place of residence, and ethnic group (Jews/non-Jews). The three DNA repair activities were measured, and an integrated DNA repair OMA (OGG1, MPG, and APE1) score was calculated for each individual. Conditional logistic regression analysis revealed that individuals in the lowest tertile of the integrated DNA repair OMA score had an increased risk of lung cancer compared with the highest tertile, with OR = 9.7; 95% confidence interval (CI), 3.1-29.8; P < 0.001, or OR = 5.6; 95% CI, 2.1-15.1; P < 0.001 after cross-validation. These results suggest that pending validation, this DNA repair panel of risk factors may be useful for lung cancer risk assessment, assisting prevention and referral to early detection by technologies such as low-dose computed tomography scanning.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. zvi.livneh@weizmann.ac.il and tamar.paz-elizur@weizmann.ac.il.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Sevilya
authors.forename: Yael
authors.initials: Y
authors.lastname: Leitner-Dagan
authors.forename: Mila
authors.initials: M
authors.lastname: Pinchev
authors.forename: Ran
authors.initials: R
authors.lastname: Kremer
authors.forename: Dalia
authors.initials: D
authors.lastname: Elinger
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.forename: Edna
authors.initials: E
authors.lastname: Schechtman
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Freedman
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.forename: Tamar
authors.initials: T
authors.lastname: Paz-Elizur
authors.forename: Zvi
authors.initials: Z
authors.lastname: Livneh
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C092514:MPEG1 protein, human; D008565:Membrane Proteins; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase