Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 7;15(1):7835.
doi: 10.1038/s41467-024-51679-x.

Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study

Abhinav Thakral #  1 , John Jw Lee #  2   3 , Tianzhichao Hou  1 , Katrina Hueniken  1 , Tom Dudding  4   5 , Mark Gormley  4   5 , Shama Virani  6 , Andrew Olshan  7 , Brenda Diergaarde  8 , Andrew R Ness  9 , Tim Waterboer  10 , Karl Smith-Byrne  6 , Paul Brennan  6 , D Neil Hayes  11 , Eleanor Sanderson  4 , M Catherine Brown  12 , Sophie Huang  12   13 , Scott V Bratman  12   13 , Anna Spreafico  12   14 , John De Almeida  15   12 , Joel C Davies  15   16 , Laura Bierut  17 , Gary J Macfarlane  18 , Pagona Lagiou  19 , Areti Lagiou  20 , Jerry Polesel  21 , Antonio Agudo  22 , Laia Alemany  22 , Wolfgang Ahrens  23 , Claire M Healy  24 , David I Conway  25 , Mari Nygard  26 , Cristina Canova  27 , Ivana Holcatova  28 , Lorenzo Richiardi  29 , Ariana Znaor  30 , David P Goldstein  15   12 , Rayjean J Hung  31   32 , Wei Xu  1   32 , Geoffrey Liu  33   34   35 , Osvaldo Espin-Garcia  1   32   36
Affiliations

Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study

Abhinav Thakral et al. Nat Commun. .

Abstract

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests. The funders had no role in the design of the study, the collection, analysis, and interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. The research was conducted independently by the authors, who are responsible for all the findings expressed in this article. The authors affirm that they have no financial or personal relationships that could have influenced the work reported in this paper. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article, and they do not necessarily represent the decisions, policies, or views of the International Agency for Research on Cancer/World Health Organization.

Figures

Fig. 1
Fig. 1. Forest plots of univariable Mendelian randomization effects of smoking and alcohol use exposures on HNSCC risk stratified by human papillomavirus (HPV) status.
Univariable estimates were obtained using summary-level data from the GWAS of a smoking initiation (n = 1232,091), b comprehensive smoking index (n = 462,690), and c drinks per week (n = 941,280) on HPV-positive HNSCC risk (n = 1105 cases and 3469 controls) and HPV-negative HNSCC (n = 2326 cases and 3469 controls). Smoking initiation estimates are reported per log odds increase, while comprehensive smoking index and drinks per week are reported per SD increase in drinks per week. Error bars represent 95% confidence intervals. All statistical tests were two-sided. CSI comprehensive smoking index, MR Mendelian randomization.
Fig. 2
Fig. 2. Forest plot of multivariable Mendelian randomization (MR) effects of lifetime smoking exposure and drinks per week on HNSCC risk stratified by human papilloma virus (HPV) status, using different MR approaches.
Effect estimates were obtained using summary-level data for drinks per week (n = 226,223) and the comprehensive smoking index (n = 226,223) on HPV-positive HNSCC risk (n = 1105 cases and 3469 controls) and HPV-negative HNSCC (n = 2326 cases and 3469 controls). Comprehensive smoking index and drinks per week estimates are reported per SD change. Error bars represent 95% confidence intervals. All statistical tests were two-sided. CSI comprehensive smoking index; “drinks” refers to alcoholic drink equivalents, IVW inverse variance-weighted, HPV−, HPV-negative, HPV+, HPV−positive, CI confidence interval.
See this image and copyright information in PMC

References

    1. Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.68, 394–424 (2018). 10.3322/caac.21492 - DOI - PubMed
    1. Jethwa, A. R. & Khariwala, S. S. Tobacco-related carcinogenesis in head and neck cancer. Cancer Metastasis Rev.36, 411–423 (2017). 10.1007/s10555-017-9689-6 - DOI - PMC - PubMed
    1. Boffetta, P., Hecht, S., Gray, N., Gupta, P. & Straif, K. Smokeless tobacco and cancer. lancet Oncol.9, 667–675 (2008). 10.1016/S1470-2045(08)70173-6 - DOI - PubMed
    1. Gandini, S. et al. Tobacco smoking and cancer: a meta‐analysis. Int. J. Cancer122, 155–164 (2008). 10.1002/ijc.23033 - DOI - PubMed
    1. Hashibe, M. et al. Evidence for an important role of alcohol-and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract. Cancer Epidemiol. Biomark. Prev.15, 696–703 (2006). 10.1158/1055-9965.EPI-05-0710 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources