Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization

A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as three of the most important modifiable lifestyle factors. Given the significant decline in smoking rates, particularly within developed countries, other potentially modifiable risk factors for head and neck cancer warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes (T2D) and hypertension have been associated with head and neck cancer risk in multiple observational studies. However, adiposity has also been correlated with smoking, with bias, confounding or reverse causality possibly explaining these findings. To overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted [IVW] method) using genetic variants which were robustly associated with adiposity, glycaemic and blood pressure traits in genome-wide association studies (GWAS). Outcome data were taken from the largest available GWAS of 6034 oral and oropharyngeal cases, with 6585 controls. We found limited evidence of a causal effect of genetically proxied body mass index (BMI; OR IVW = 0.89, 95% CI 0.72-1.09, p = 0.26 per 1 standard deviation in BMI [4.81kg/m(2)]) on oral and oropharyngeal cancer risk. Similarly, there was limited evidence for related traits including T2D and hypertension. Small effects cannot be excluded given the lack of power to detect them in currently available GWAS.

Automated summary

A recent study suggests that smoking, alcohol consumption, and obesity are important modifiable lifestyle factors contributing to cancer. However, further investigation is needed to identify other potential risk factors for head and neck cancer, especially in light of the declining smoking rates. The study conducted Mendelian randomization using genetic variants associated with adiposity, diabetes, and hypertension to explore their causal effects on oral and oropharyngeal cancer risk. The findings suggested limited evidence of a causal relationship between body mass index, diabetes, hypertension, and the risk of head and neck cancer.