title: Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study.
abstract: OBJECTIVE
  Patients with type 2 diabetes mellitus (DM) may be at increased colorectal cancer (CRC) risk. However, existing data are inconsistent. We investigated CRC risks, overall and by anatomic subsite, within a population-based inception cohort of clinically confirmed type 2 DM subjects.
  
  
  METHODS
  All residents of Rochester, Minnesota who first met standardized criteria for type 2 DM from 1970 to 1994 (997 men and 978 women) were identified and followed forward in time until emigration, death, or December 31, 1999. Incident CRC cases were identified by review of inpatient and outpatient medical records. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated to compare CRC incidence within the type 2 DM inception cohort with previously published rates for the Rochester general population.
  
  
  RESULTS
  Over 19,158 person-years of follow-up, 51 incident CRC cases were identified within the type 2 DM cohort, while only 36.8 cases were expected (SIR = 1.39, 95% CI 1.03-1.82). Among men, type 2 DM was associated with increased overall (SIR = 1.67, 95% CI 1.16-2.33) and proximal (SIR = 1.96, 95% CI 1.16-3.10) CRC risks; distal CRC risk was also increased, but the point estimate was not statistically significant (SIR = 1.43, 95% CI 0.82-2.32). Among women, type 2 DM was not a risk factor for overall, proximal, or distal CRC (SIR = 1.03, 95% CI 0.60-1.66; SIR = 1.17, 95% CI 0.58-2.09; and SIR = 0.74, 95% CI 0.24-1.72, respectively). Within the type 2 DM cohort, current and former cigarette smokers were at higher CRC risk (SIR = 1.77, 95% CI 1.24-2.47) than never smokers (SIR = 0.99, 95% CI 0.57-1.61) and the interaction between type 2 DM and cigarette smoking status was statistically significant (p= 0.05).
  
  
  CONCLUSIONS
  In this population-based, retrospective cohort study, clinically confirmed type 2 DM was associated with increased CRC risk, predominantly among men. Cigarette smoking appeared to positively modify DM-associated CRC risk, which to our knowledge has not been previously reported. These data suggest that further investigation of potential interactions between endogenous and exogenous factors involved in colorectal carcinogenesis may help to clarify the magnitude and extent of CRC risk experienced by persons with type 2 DM.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Leibson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Amit K
authors.initials: AK
authors.lastname: Gupta
authors.forename: David A
authors.initials: DA
authors.lastname: Ahlquist
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Melton
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
mesh_terms: D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors