Projects per year
Abstract
Background:
Adiposity has been associated with an increased risk of head and neck cancer (HNC). Although body mass index (BMI) has been inversely associated with HNC risk among smokers, this is likely due to confounding. Previous Mendelian randomization (MR) studies could not fully discount causality between adiposity and HNC. Hence, we aimed to revisit this using the largest genome-wide association study (GWAS) of HNC available, which has more granular data on HNC subsites.
Methods:
We assessed the genetically predicted effects of BMI (N=806,834), waist-to-hip ratio (WHR; N=697,734) and waist circumference (N=462,166) on the risk of HNC (N=12,264 cases) and its subsites using a two-sample MR framework. We used inverse variance weighted (IVW) MR and multiple sensitivity analyses, including multivariable MR (MVMR), to explore the direct effects of the adiposity measures on HNC, while accounting for smoking behaviour (a well-known HNC risk factor).
Results:
In univariable MR, higher genetically predicted BMI increased the risk of overall HNC (IVW OR = 1.17 per 1-SD higher BMI, 95% CI 1.02–1.34). However, the IVW effect was attenuated when smoking was included in the MVMR model (OR accounting for comprehensive smoking index = 0.96 per 1-SD higher BMI, 95% CI 0.80–1.15). Furthermore, we did not find a link between genetically predicted WHR (IVW OR = 1.05 per 1-SD higher WHR, 95% CI 0.89–1.24) or waist circumference and HNC risk (IVW OR = 1.01 per 1-SD higher waist circumference, 95% CI 0.85–1.21).
Conclusions:
Our findings suggest that adiposity does not play a major role in HNC risk.
Adiposity has been associated with an increased risk of head and neck cancer (HNC). Although body mass index (BMI) has been inversely associated with HNC risk among smokers, this is likely due to confounding. Previous Mendelian randomization (MR) studies could not fully discount causality between adiposity and HNC. Hence, we aimed to revisit this using the largest genome-wide association study (GWAS) of HNC available, which has more granular data on HNC subsites.
Methods:
We assessed the genetically predicted effects of BMI (N=806,834), waist-to-hip ratio (WHR; N=697,734) and waist circumference (N=462,166) on the risk of HNC (N=12,264 cases) and its subsites using a two-sample MR framework. We used inverse variance weighted (IVW) MR and multiple sensitivity analyses, including multivariable MR (MVMR), to explore the direct effects of the adiposity measures on HNC, while accounting for smoking behaviour (a well-known HNC risk factor).
Results:
In univariable MR, higher genetically predicted BMI increased the risk of overall HNC (IVW OR = 1.17 per 1-SD higher BMI, 95% CI 1.02–1.34). However, the IVW effect was attenuated when smoking was included in the MVMR model (OR accounting for comprehensive smoking index = 0.96 per 1-SD higher BMI, 95% CI 0.80–1.15). Furthermore, we did not find a link between genetically predicted WHR (IVW OR = 1.05 per 1-SD higher WHR, 95% CI 0.89–1.24) or waist circumference and HNC risk (IVW OR = 1.01 per 1-SD higher waist circumference, 95% CI 0.85–1.21).
Conclusions:
Our findings suggest that adiposity does not play a major role in HNC risk.
| Original language | English |
|---|---|
| Article number | RP106075 |
| Number of pages | 28 |
| Journal | eLife |
| Volume | 14 |
| DOIs | |
| Publication status | Published - 9 Oct 2025 |
Research Groups and Themes
- ICEP
- Bristol Population Health Science Institute
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Integrative Epidemiology Unit
Tilling, K. M. (Principal Investigator)
1/04/23 → 31/03/28
Project: Research
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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research