Type 2 Diabetes, Antidiabetic Medications, and Colorectal Cancer Risk: Two Case-Control Studies from Italy and Spain.

Valentina Rosato,Federica E Pisa,Jerry Polesel,Cristina Bosetti,Carlo La Vecchia,Elisabet Guinó,Manolis Kogevinas,Cristina M Villanueva,Esther Gracia-Lavedan,Alessandra Tavani,Fabio Barbone,Diego Serraino,Victor Moreno,Gemma Castaño-Vinyals

doi:10.3389/fonc.2016.00210

Abstract

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. We examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering also duration of exposures. 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. 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). 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.

Highlights

Colorectal cancer is the third most common cancer and the fourth leading cause of cancer death worldwide, and the fourth and second, respectively, in Europe [1, 2]
159 (13.9%) of cases and 188 (11.8%) of controls reported a diagnosis of type 2 diabetes, corresponding to a multivariable odds ratios (ORs) of 1.21
The OR of colorectal cancer was higher for a duration of diabetes of ≥15 years, but the trend in risk for increasing duration was not significant (p-value = 0.10)

Summary

Introduction

Colorectal cancer is the third most common cancer and the fourth leading cause of cancer death worldwide, and the fourth and second, respectively, in Europe [1, 2]. Type 2 diabetes mellitus has been associated with an excess risk of colorectal cancer [7,8,9,10], as well as with of cancers related to metabolic factors [11, 12]. Only a few studies considered the timing of the disease in relation to colorectal cancer diagnosis, reporting no clear trend in risk [9]. Type 2 diabetes mellitus has been associated with an excess risk of colorectal cancer, the time–risk relationship is unclear, and there is limited information on the role of antidiabetic medications. Aim: We examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering duration of exposures

Objectives

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Results

Conclusion