1. Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study.
- Author
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Thakral A, Lee JJ, Hou T, Hueniken K, Dudding T, Gormley M, Virani S, Olshan A, Diergaarde B, Ness AR, Waterboer T, Smith-Byrne K, Brennan P, Hayes DN, Sanderson E, Brown MC, Huang S, Bratman SV, Spreafico A, De Almeida J, Davies JC, Bierut L, Macfarlane GJ, Lagiou P, Lagiou A, Polesel J, Agudo A, Alemany L, Ahrens W, Healy CM, Conway DI, Nygard M, Canova C, Holcatova I, Richiardi L, Znaor A, Goldstein DP, Hung RJ, Xu W, Liu G, and Espin-Garcia O
- Subjects
- Humans, Male, Female, Risk Factors, Papillomaviridae genetics, Middle Aged, Case-Control Studies, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis, Alcohol Drinking adverse effects, Head and Neck Neoplasms virology, Head and Neck Neoplasms genetics, Head and Neck Neoplasms epidemiology, Smoking adverse effects, Papillomavirus Infections virology, Papillomavirus Infections epidemiology, Squamous Cell Carcinoma of Head and Neck virology, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck epidemiology
- 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., (© 2024. The Author(s).)
- Published
- 2024
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