title: The Effect of Polymorphisms in DNA Repair Genes and Carcinogen Metabolizers on Leukocyte Telomere Length: A Cohort of Healthy Spanish Smokers.
abstract: BACKGROUND
  Smoking implies exposure to carcinogenic agents that causes DNA damage, which could be suspected to enhance telomere attrition. To protect and deal with DNA damage, cells possess mechanisms that repair and neutralize harmful substances. Polymorphisms altering DNA repair capacity or carcinogen metabolism may lead to synergistic effects with tobacco carcinogen-induced shorter telomere length independently of cancer interaction. The aim of this study was to explore the association between leukocyte telomere length (LTL) and several genetic polymorphisms in DNA repair genes and carcinogen metabolizers in a cohort of healthy smokers.
  
  
  METHODS
  We evaluated the effect of six genetic polymorphisms in cytochrome P1A1 (Ile462Val), XRCC1 (Arg399Gln), APEX1 (Asp148Glu), XRCC3 (Thr241Met), and XPD (Asp312Asn; Lys751Gln) on LTL in a cohort of 145 healthy smokers in addition to smoking habits.
  
  
  RESULTS
  Logistic regression analysis showed an association between XRCC1 399Gln allele and shorter telomere length (OR = 5.03, 95% CI = 1.08% to 23.36%). There were not association between the rest of polymorphisms analyzed and LTL.
  
  
  CONCLUSIONS
  Continuous exposure to tobacco could overwhelm the DNA repair machinery, making the effect of the polymorphisms that reduce repair capacity more pronounced. Analyzing the function of smoking-induced DNA-repair genes and LTL is an important goal in order to identify therapeutic targets to treat smoking-induced diseases.
authors.affiliation: Department of Biomedical Sciences, Universidad Europea, Madrid, Spain; zoraida.verde@uem.es.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Verde
authors.affiliation: Department of Biomedical Sciences, Universidad Europea, Madrid, Spain; Department of Occupational Medicine, Grupo Banco Popular, Madrid, Spain;
authors.forename: Luis
authors.initials: L
authors.lastname: Reinoso-Barbero
authors.affiliation: Department of Biomedical Sciences, Universidad Europea, Madrid, Spain;
authors.forename: Luis
authors.initials: L
authors.lastname: Chicharro
authors.affiliation: Department of Neumology, Hospital Guadalajara, Guadalajara, Spain;
authors.forename: Pilar
authors.initials: P
authors.lastname: Resano
authors.affiliation: Department of Neumology, Hospital Carlos III, Madrid, Spain;
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sánchez-Hernández
authors.affiliation: Department of Neumology, Hospital Gregorio Marañón, Madrid, Spain;
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Rodríguez González-Moro
authors.affiliation: Department of Toxicology and Health Sanitary, Universidad Complutense, Madrid, Spain;
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandrés
authors.affiliation: School of Doctoral Studies and Research, Universidad Europea, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
authors.affiliation: School of Doctoral Studies and Research, Universidad Europea, Madrid, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002273:Carcinogens / Q000378:metabolism*; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D016615:Telomere / Q000235:genetics*; D044465:White People / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D002273:Carcinogens; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human