title: Type 2 Diabetes, Antidiabetic Medications, and Colorectal Cancer Risk: Two Case-Control Studies from Italy and Spain.
abstract: BACKGROUND
  Type 2 diabetes mellitus has been associated with an excess risk of colorectal cancer, although the time-risk relationship is unclear, and there is limited information on the role of antidiabetic medications.
  
  
  OBJECTIVE
  We examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering also duration of exposures.
  
  
  METHODS
  We analyzed data derived from two companion case-control studies conducted in Italy and Spain between 2007 and 2013 on 1,147 histologically confirmed colorectal cancer cases and 1,594 corresponding controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional multiple logistic regression models, adjusted for socioeconomic factors and major potential confounding factors.
  
  
  RESULTS
  Overall, 14% of cases and 12% of controls reported a diagnosis of diabetes, corresponding to an OR of colorectal cancer of 1.21 (95% CI 0.95-1.55). The OR was 1.49 (95% CI 0.97-2.29) for a duration of diabetes of at least 15 years. The OR was 1.53 (95% CI 1.06-2.19) for proximal colon cancer, 0.94 (95% CI 0.66-1.36) for distal colon cancer, and 1.32 (95% CI 0.94-1.87) for rectal cancer. In comparison with no use, metformin use was associated with a decreased colorectal cancer risk (OR 0.47, 95% CI 0.24-0.92), while insulin use was associated with an increased risk (OR 2.20, 95% CI 1.12-4.33); these associations were stronger for longer use (OR 0.36 and 8.18 for ≥10 years of use of metformin and insulin, respectively).
  
  
  CONCLUSIONS
  This study shows evidence of a positive association between diabetes and colorectal cancer, mainly proximal colon cancer. Moreover, it indicates a negative association between colorectal cancer and metformin use and a positive association for insulin use.
authors.affiliation: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rosato
authors.affiliation: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tavani
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gracia-Lavedan
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Cancer Prevention and Control Program, Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO)-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Guinó
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Villanueva
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, IRCCS , Aviano , Italy.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, IRCCS , Aviano , Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Serraino
authors.affiliation: SOC Igiene ed Epidemiologia Clinica, Azienda Ospedaliero Universitaria di Udine , Udine , Italy.
authors.forename: Federica E
authors.initials: FE
authors.lastname: Pisa
authors.affiliation: SOC Igiene ed Epidemiologia Clinica, Azienda Ospedaliero Universitaria di Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Barbone
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Cancer Prevention and Control Program, Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO)-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan , Milan , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosetti
keywords: antidiabetic medications; colorectal cancer; diabetes; insulin; metformin; risk factor