Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge. 1. Diabetes and Cancer The prevalence of diabetes in newly diagnosed cancer patients is reported to be from 8% to 18% [1]. A meta-analysis of 12 cohort studies reported a significant pooled adjusted risk ratio (RR) of all-cancer incidence (RR = 1.10, 95% CI, and 1.04 to 1.17). The increased risk was observed for both men (RR = 1.14, CI, and 1.06 to 1.23) and women (RR = 1.18, CI, and 1.08 to 1.28) [2]. An increase for site-specific cancer incidence has also been described in many systematic reviews and meta-analyses. Deng et al. reported a 26% increase in the incidence of colorectal cancer. The rate was similar in both women and men. These results were obtained from eight case-control and 16 cohort studies without heterogeneity between studies ( ) [3]. Parallel to these results, Jiang et al. also described an increased incidence of colorectal cancer in a systematic review of 41 cohort studies (summary of relative risk 1.27, 95% CI: 1.21–1.34) [4]. Although the studies showed significant heterogeneity ( , ), the incidence seems not to be affected by sex (RR = 1.25, 95% CI: 1.19–1.14 in men, and RR = 1.34, 95% CI: 1.22–1.47 in women) [5]. Breast cancer has also been shown to be more prevalent in women with type 2
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