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Mendelian Randomization Study Questions Role of Obesity in Head and Neck Cancer Risk

Despite research linking obesity and related metabolic disorders to head and neck cancers (HNCs), metabolic traits may not be effective modifiable risk factors for these malignancies, according to a study appearing this week in eLife. Obesity, type 2 diabetes, and hypertension have all been associated with HNC risk in observational studies, but these links could potentially be explained by selection bias, confounders such as tobacco smoking, and reverse causation. In their new study, investigators from the University of Bristol performed two-sample Mendelian randomization using genetic variants robustly associated with adiposity, as well as glycemic and blood pressure traits, in genome-wide association studies. They find limited evidence to support a causal role of genetically predicted metabolic traits in oral and oropharyngeal cancer, suggesting the risk may have been previously overestimated in observational studies. As such, the modification metabolic traits may not be an effective prevention strategy in HNC. Still, the study's authors caution that small effects cannot be excluded given the lack of power to detect them in currently available HNC genome-wide association studies.