Diabetes mellitus, metformin and head and neck cancer

Highlights

• There was an inverse association between diabetes and head and neck cancer.

• The inverse association may be explained by metformin, since in separated analysis by use of metformin in diabetic patients there was protection for head and neck cancer only among metformin users.

Summary

Introduction

Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated with some cancers. However, studies on the association between diabetes mellitus and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial results. The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC.

Material and methods

This case-control study was conducted within the framework of the Brazilian Head and Neck Genome Project in 2011–2014. The study included 1021 HNC cases with histologically confirmed squamous cell carcinoma of the head and neck admitted to five large hospitals in São Paulo state. A total of 1063 controls were selected in the same hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression.

Results

Diabetic participants had a decreased risk of HNC (OR = 0.68; 95% CI: 0.49–0.95) than non-diabetic participants, and this risk was further decreased among diabetic metformin users (OR = 0.54; 95% CI: 0.29–0.99). Diabetic metformin users that were current smokers (OR = 0.13; 95% CI: 0.04–0.44) or had an alcohol consumption of >40 g/day (OR = 0.31; 95% CI: 0.11–0.88) had lower risk of HNC than equivalent non-diabetic participants.

Conclusion

The risk of HNC was decreased among diabetic participants; metformin use may at least partially explain this inverse association.

Introduction

Head and neck cancer (HNC) includes tumours of the oral cavity, oropharynx, hypopharynx, and larynx. Nasopharyngeal cancer is also a HNC sub-site but is usually considered a separate disease with a distinct aetiology and particular characteristics [1]. Approximately 600,000 cases of HNC are diagnosed each year, and HNC accounts for 4% of cancer mortality worldwide [2]. More than 90% of HNC are squamous cell carcinoma [3]. The main risk factors associated with HNC are smoking and alcohol consumption, and the interaction between these factors can increase the risk of HNC [4]. Other risk factors include poor oral health, diet, genetic factors, low body mass index (BMI), and occupational factors [5], [6], [7], [8].

The association between diabetes mellitus (DM) and the increased risk of certain cancers, such as liver, pancreatic, colon, kidney, bladder, endometrial, and breast cancer, is well established [9], [10], [11], while the risk of prostate cancer is decreased among diabetic patients [11], [12]. Although some studies with DM has also been associated with HNC, these results are still controversial. In some studies, diabetic patients had an increased risk of cancer at some HNC sub-sites [10], [13], [14], [15], while in other studies this risk was decreased [9], [16].

One possible explanation for inverse association between DM and some kinds of cancers is metformin use among diabetic patients. Metformin is a medication used to control Type 2 DM and can inhibit cell proliferation, which has been inversely associated with cancer risk [11], [17]. It has been shown that metformin users have a reduced risk of colorectal, liver, lung, and prostate cancer [18], [19], [20]. Studies on the association between DM and the risk of HNC that take into account metformin use have also reported conflicting results. A Taiwanese study reported a decreased risk of HNC among metformin users (adjusted hazard ratio = 0.66; 95% confidence interval [CI] 0.55–0.79) [21], while another study in the United Kingdom reported no association [22].

The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC.