title: APC and KRAS mutations in distal colorectal polyps are related to smoking habits in men: results of a cross-sectional study.
abstract: BACKGROUND
  The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis.
  
  
  METHODS
  A total of 623 asymptomatic male (mean age: 53 years; 50-65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models.
  
  
  RESULTS
  Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2-3.6; p<0.05) and HP (OR 5.4; 95% CI 2.6- 11.1; p<0.05). No differences in CRC were observed. There was a dose-response relationship with the number of cigarettes smoked. The risk of developing AP or HP decreased after smoking cessation, even among heavy smokers (≥20 packs/year). KRAS mutations were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4; p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers, but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no differences in MSI between smokers and non-smokers.
  
  
  CONCLUSIONS
  Cigarette smoking is associated with a higher risk of developing both HP and AP and a higher prevalence of mutations in APC and KRAS.
authors.affiliation: Department of Gastroenterology, Instituto Valenciano de Oncología, C/ Profesor Beltrán Báguena 8, Valencia, Spain. fernandomarju@gmail.com
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Martos
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Quintana
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart
authors.forename: Francisco
authors.initials: F
authors.lastname: Ińiguez
authors.forename: Vicente
authors.initials: V
authors.lastname: Guillem
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D018256:Adenomatous Polyps / Q000453:epidemiology / Q000235:genetics; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D017491:Genes, APC; D006801:Humans; D007417:Intestinal Polyps / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins