World Cancer Research Fund (WCRF): How do metabolic traits effect risk and survival from head and neck cancer?

Background

According to the World Health Organization (WHO), at least 40% of all cancer cases may be preventable, with tobacco smoking, alcohol consumption and obesity identified as three of the most important modifiable lifestyle factors. For head and neck cancers (HNC), smoking and alcohol explain approximately 64%-70% of the population attributable fraction, depending on site, leaving ~30% of risk unexplained. For oropharynx cancer, human papilloma virus is a major risk factor, with attributable fractions ranging from 10-80%. The emerging importance of adiposity and related metabolic traits in cancer is evidenced through its association with 11 cancers. In 2018, the WCRF concluded that being overweight or living with obesity increases the risk of HNC and recent studies point to low BMI at HNC diagnoses being related to poorer outcomes. It is important to determine the effect of metabolic traits on HNC risk and survival, but limitations across study designs have prevented a comprehensive understanding. Here, we triangulate evidence of metabolic traits on HNC risk and survival using multiple study designs.

Hypothesis and Objectives

We hypothesize that metabolic traits can act independently or interact with other known risk factors to modulate risk of and survival from HNC. The objective of this study is to triangulate evidence for the effect of metabolic traits on HNC risk and survival using a range of study designs, with a specific focus on risk factor interactions.

Settings and Methods

For observational analyses, multivariable logistic regression and flexible parametric survival models will be used to assess BMI with HNC risk and survival. Interaction terms with smoking, alcohol consumption and viral status will be modelled and tested for heterogeneity. Individual SNPs in the mitochondrial genome will be tested for association with risk/survival using a logistic regression model.

For genetic analyses, a Mendelian randomization approach will be implemented using established genetic instruments for individual metabolic traits. Odds and Hazards ratios will be calculated for each metabolic trait to determine their causal effect on HNC risk and survival. The MR approach will be extended to assess mediators and interaction of smoking, alcohol and viral infection with metabolic traits.

Impact

The study findings will provide evidence on whether or not metabolic traits do play a role in risk or survival for this disease. This could be used to support future prevention strategies or help stratify HNC patients based on survival. With the success of smoking initiatives in reducing cancer rates, and recent advances in ‘medical’ weight loss strategies, equitable programmes for intentional weight loss with cancer risk as an outcome could be supported with this evidence. Furthermore, identifying specific metabolic profiles which contribute to improved survival may lead to customised packages of care to get HNC patients ‘ready’ for treatment.