title: Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer.
abstract: BACKGROUND
  Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1,CYP2A6) or in DNA repair (XRCC1,APEX1,XRCC3andXPD) in breast cancer development.
  
  
  METHODS
  We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women.
  
  
  RESULTS
  We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (allPtrend< 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and theCYP1A1 Ile462Ilegenotype was associated with increased risk of breast cancer (OR = 7.12 (1.98-25.59)).
  
  
  CONCLUSIONS
  Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis thatCYP1A1 Ile462Val, in association with long periods of active smoking, could be a breast cancer risk factor.
authors.affiliation: Department of Biomedical Sciences, European University, Madrid 28670, Spain. zoraida.verde@universidadeuropea.es.
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Verde
authors.affiliation: School of Doctoral Studies & Research, European University, Madrid 28670, Spain. catalina.santiago@universidadeuropea.es.
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.affiliation: Cátedra Complutense Diagnostic and Innovation, Universidad Complutense, Madrid 28040, Spain. luismi.chicharro@gmail.com.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Chicharro
authors.affiliation: Department of Biomedical Sciences, European University, Madrid 28670, Spain. luis.reinoso@universidadeuropea.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Reinoso-Barbero
authors.affiliation: Centro de Patología de la Mama-Fundación Tejerina, Madrid 28003, Spain. alejandro.tejerina@fjd.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tejerina
authors.affiliation: Cátedra Complutense Diagnostic and Innovation, Universidad Complutense, Madrid 28040, Spain. fbandres@med.ucm.es.|Department of Toxicology and Health Sanitary, Complutense University of Madrid, Madrid 28040, Spain. fbandres@med.ucm.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandrés
authors.affiliation: School of Doctoral Studies & Research, European University, Madrid 28670, Spain. felix.gomez@universidadeuropea.es.
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C569463:CYP1A1 protein, human; C585710:CYP2A6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; D051759:Xeroderma Pigmentosum Group D Protein; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C497292:ERCC2 protein, human
keywords: CYP1A; DNA repair genes; breast cancer; long-term smoking