title: Cigarette smoking and colorectal cancer: long-term, subsite-specific risks in a cohort study of postmenopausal women.
abstract: OBJECTIVE
  Cigarette smoking is a putative risk factor for colorectal cancer (CRC). However, long-term CRC risk estimates among female smokers remain limited and inconsistent. The goal of this prospective study was to assess cigarette smoking and CRC risk, overall and by anatomic subsite, among postmenopausal women.
  
  
  METHODS
  Data were drawn from a large population-based cohort (n = 41836) of randomly selected women, age 55-69 years at baseline (Iowa Women's Health Study). Cigarette smoking and other CRC risk factors were characterized at baseline (1986). Incident (n = 869) and fatal (n = 249) CRC cases were identified through December 31, 1999. CRC risks were estimated using Cox proportional hazards regression models.
  
  
  RESULTS
  Compared with never smokers, ever smokers had slightly increased risks for both incident (relative risk [RR], 1.17; 95% confidence interval [CI], 1.00-1.36) and fatal (RR, 1.31; 95% CI, 0.98-1.74) CRC in multivariate analyses. Incident CRC risks increased progressively by lengthening induction period (P trend=0.01), reaching a 30% increase (RR, 1.30; 95% CI, 1.04-1.63) after age 45 years. By anatomic subsite, ever smoked cigarettes and induction period were more strongly associated with incident proximal CRC (P = 0.03 and P trend = 0.03, respectively) than incident distal CRC (P=0.44 and P trend=0.10, respectively).
  
  
  CONCLUSIONS
  In this long-term cohort study of postmenopausal women, cigarette smoking was positively associated with CRC risk. Onset of smoking in the distant past appeared to confer the greatest risk, especially for incident proximal CRC. These data support a potential subsite-specific role for cigarette smoking in colorectal carcinogenesis, at least among women. Based on emerging data, an epigenetic pathway for smoking-induced CRC is proposed.
authors.affiliation: Divisions of Gastroenterology and Hepatology and Epidemiology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Deann
authors.initials: D
authors.lastname: Lazovich
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation