In a recent study published in BMC Medical Genomics, researchers assessed the association between obesity and head and neck cancer risk.

Study: Obesity and head and neck cancer risk: a mendelian randomization study. Image Credit: Pormezz/Shutterstock.com

Background

Head and neck cancer, an umbrella term for cancers of the salivary glands, sinus, pharynx, larynx, oral cavity, and oropharynx, globally accounts for over 7% of cancers and 5% of cancer deaths. Alcohol consumption, smoking status, and high-risk types of human papillomavirus (HPV) are the major risk factors.

Obesity has been associated with numerous cancers; it is considered a common and modifiable risk factor. Recent studies suggest that obesity is associated with head and neck cancer.

One study showed a negative association between head and neck cancer risk and obesity; another found no association between obesity and head and neck cancer incidence.

Besides, a positive association has been observed between body mass index (BMI) and the risk of head and neck cancer in non-smokers. However, the inconsistencies observed in observational studies might have been influenced by reverse causality or confounding.

By contrast, Mendelian randomization (MR) analyses, which use genetic variants to assess the causal associations, may reduce bias from confounding or reverse causality.

About the study

In the present study, researchers explored the causal associations between head and neck cancer and obesity by performing a two-sample MR analysis. They used public data from genome-wide association studies (GWASs). Obesity- and head and neck cancer-associated single nucleotide polymorphisms (SNPs) were retrieved from GWASs and used as instrumental variables.

Exposures included waist-to-hip ratio (WHR), BMI, lean body mass, trunk fat mass, whole-body fat mass, BMI adjusted for smoking, and WHR adjusted for smoking and BMI.

Outcomes were 1) overall head and neck cancer, 2) oropharyngeal cancer, 3) oral cavity cancer, and 4) oropharyngeal and oral cavity cancer. SNPs with genome-wide significance and not in linkage disequilibrium were selected, whereas those with minor allele frequency below 0.01 were excluded.

The MR-Egger intercept test tested horizontal pleiotropy. Individual MR effect estimates were computed for each SNP. The association of obesity with head and neck cancer was estimated using MR-Egger, weighted mode, weighted median, inverse-variance weighted (IVW), and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods.

Cochran’s Q test was used to evaluate heterogeneity, and leave-one-out (sensitivity) analyses assessed the reliance of MR on a given SNP. Bidirectional MR analysis was performed to examine reverse causal associations.

Odds ratios and 95% confidence intervals were computed; p-values < 0.00139 were statistically significant, and those between 0.00139 and 0.05 were deemed to have suggestive significance.

Findings

Seventy-eight and 28 SNPs associated with BMI and WHR, respectively, were identified for overall head and neck or oropharyngeal cancer. Likewise, 75 BMI-associated SNPs and 29 WHR-associated SNPs were included for the oral cavity cancer outcome. No horizontal pleiotropy or heterogeneity was observed.

A negative association was observed between genetically predicted BMI and overall head and neck cancer risk. This association achieved statistical significance in MR-PRESSO, weighted median, and IVW analyses and suggestive significance in weighted mode and MR-Egger analyses.

BMI might be negatively associated with the risk of oropharyngeal, oral cavity, or oral cavity and oropharyngeal cancer.

BMI adjusted for smoking showed a negative association only with overall head and cancer risk. WHR might be negatively associated with overall head and neck cancer risk. No additional associations were observed between other exposures and outcomes. The sensitivity analysis indicated that any individual SNP did not cause the association. Besides, reverse causal association was not detected.

Conclusions

The findings showed a negative association between BMI-related obesity and overall head and neck cancer risk, remaining significant even after adjusting for smoking. However, WHR-related obesity was unrelated to head and neck cancer risk.

Notably, the populations included in GWASs were of European descent, limiting generalizability. More studies are required to identify causal associations between obesity and the type of head and neck cancer.

Journal reference:

• Gui, L. et al. (2023) "Obesity and head and neck cancer risk: a mendelian randomization study", BMC Medical Genomics, 16(1). doi: 10.1186/s12920-023-01634-4. https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-023-01634-4