Thakral, Abhinav and Lee, John JW. and Hou, Tianzhichao and Hueniken, Katrina and Dudding, Tom and Gormley, Mark and Virani, Shama and Olshan, Andrew and Diergaarde, Brenda and Ness, Andrew R. and Waterboer, Tim and Smith-Byrne, Karl and Brennan, Paul and Hayes, D. Neil and Sanderson, Eleanor and Brown, M. Catherine and Huang, Sophie and Bratman, Scott V. and Spreafico, Anna and De Almeida, John and Davies, Joel C. and Bierut, Laura and Macfarlane, Gary J. and Lagiou, Pagona and Lagiou, Areti and Polesel, Jerry and Agudo, Antonio and Alemany, Laia and Ahrens, Wolfgang and Healy, Claire M. and Conway, David I. and Nygard, Mari and Canova, Cristina and Holcatova, Ivana and Richiardi, Lorenzo and Znaor, Ariana and Goldstein, David P. and Hung, Rayjean J. and Xu, Wei and Liu, Geoffrey and Espin-Garcia, Osvaldo (2024) Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study. Nature Communications, 15: 7835. ISSN 2041-1723

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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.

Information
Title Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study
Creators Thakral, Abhinav and Lee, John JW. and Hou, Tianzhichao and Hueniken, Katrina and Dudding, Tom and Gormley, Mark and Virani, Shama and Olshan, Andrew and Diergaarde, Brenda and Ness, Andrew R. and Waterboer, Tim and Smith-Byrne, Karl and Brennan, Paul and Hayes, D. Neil and Sanderson, Eleanor and Brown, M. Catherine and Huang, Sophie and Bratman, Scott V. and Spreafico, Anna and De Almeida, John and Davies, Joel C. and Bierut, Laura and Macfarlane, Gary J. and Lagiou, Pagona and Lagiou, Areti and Polesel, Jerry and Agudo, Antonio and Alemany, Laia and Ahrens, Wolfgang and Healy, Claire M. and Conway, David I. and Nygard, Mari and Canova, Cristina and Holcatova, Ivana and Richiardi, Lorenzo and Znaor, Ariana and Goldstein, David P. and Hung, Rayjean J. and Xu, Wei and Liu, Geoffrey and Espin-Garcia, Osvaldo
Identification Number 10.1038/s41467-024-51679-x
Date 7 September 2024
Divisions College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Publisher Nature Research
Additional Information This study was funded in part by NIH/NIDCR R01 DE025712 (to P.B., B.D., and D.N.H.). Genotyping of the HNSCC cases and controls was performed at the Center for Inherited Disease Research (CIDR) and funded by NIH/NIDCR 1X01HG007780-0. The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission’s fifth framework program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). We thank Dr. Wolfgang Ahrens, PhD (Universität Bremen, Germany) for his support in ARCAGE study. The Carolina Head and Neck Cancer Epidemiology (CHANCE) study was supported in part by the National Cancer Institute (R01-CA90731). The Head and Neck 5000 study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Program Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Core funding was also provided through awards from Above and Beyond, University Hospitals Bristol and Weston Research Capability Funding, and the NIHR Senior Investigator award to Professor Andy Ness. Human papillomavirus (HPV) serology was supported by a Cancer Research UK Program Grant, the Integrative Cancer Epidemiology Program (grant number: C18281/A19169). The University of Pittsburgh head and neck cancer case-control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The MSH-PMH study is supported by the Canadian Cancer Society Research Institute, and CIHR Canada Research Chair to R.J.H. J.P. was partially supported by the Italian Ministry of Health “Ricerca Corrente”. G.L. is funded by the Alan B. Brown Chair in Molecular Genomics and the Lusi Wong Foundation Fund. This study was supported by the Princess Margaret Cancer Center Head &amp; Neck Translational Program, with philanthropic funds from the Wharton Family, Joe’s Team, and Gordon Tozer. Computations were performed on the Niagara supercomputer at the SciNet HPC Consortium. SciNet is funded by the Canada Foundation for Innovation, the Government of Ontario, the Ontario Research Fund—Research Excellence, and the University of Toronto.
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Date Deposited 11 Jun 2025 16:35
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