title: Associations between smoking, alcohol consumption, and colorectal cancer, overall and by tumor microsatellite instability status.
abstract: BACKGROUND
  Both smoking and alcohol consumption have been associated with modestly increased risks of colorectal cancer (CRC). Reports have suggested that these associations may differ by tumor molecular subtype, with stronger associations for microsatellite unstable (MSI-H) tumors.
  
  
  METHODS
  We used a population-based case-unaffected sibling design including 2,248 sibships (2,253 cases; 4,486 siblings) recruited to the Colon Cancer Family Registry to evaluate the association between smoking, alcohol consumption, and CRC. Associations were assessed using conditional logistic regression, treating sibship as the matching factor.
  
  
  RESULTS
  Although there were no statistically significant associations between any smoking variable and CRC overall, smoking did confer an increased risk of certain types of CRC. We observed an association between pack-years of smoking and rectal cancer [odds ratio (OR), 1.85; 95% confidence interval (CI), 1.23-2.79 for >40 pack-years versus nonsmokers; P(trend) = 0.03], and there was an increased risk of MSI-H CRC with increasing duration of smoking (OR, 1.94; 95% CI, 1.09-3.46 for >30 years of smoking versus nonsmokers). Alcohol intake was associated with a modest increase in risk for CRC overall (OR, 1.21; 95% CI, 1.03-1.44 for 12+ drinks per week versus nondrinkers), with more marked increases in risk for MSI-L CRC (OR, 1.85; 95% CI, 1.06-3.24) and rectal cancer (OR, 1.48; 95% CI, 1.08-2.02).
  
  
  CONCLUSIONS
  We found associations between cigarette smoking and increased risks of rectal cancer and MSI-H CRC. Alcohol intake was associated with increased risks of rectal cancer and MSI-L CRC. These results highlight the importance of considering tumor phenotype in studies of risk factors for CRC.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA. poynt006@umn.edu
authors.forename: Jenny N
authors.initials: JN
authors.lastname: Poynter
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Siegmund
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.forename: Paul
authors.initials: P
authors.lastname: Limburg
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D055815:Young Adult