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

Abhinav ThakralJohn J W LeeTianzhichao HouKatrina HuenikenTom DuddingMark GormleyShama ViraniAndrew OlshanBrenda DiergaardeAndrew R NessTim WaterboerKarl Smith ByrnePaul BrennanDavid Neil HayesEleanor C M SandersonM Catherine BrownSophie HuangScott V BratmanAnna SpreaficoJohn De AlmeidaJoel C DaviesLaura J BierutGary J MacfarlanePagona LagiouAreti LagiouJerry PoleselAntonio AgudoLaia AlemanyWolfgang AhrensClaire M HealyDavid I ConwayMari NygardCristina CanovaIvana HolcatovaLorenzo RichiardiAriana ZnaorDavid Paul GoldsteinRayjean J HungWei XuGeoffrey LiuOsvaldo Espin-Garcia
Published in: Nature communications (2024)
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.
Keyphrases
  • high grade
  • cervical cancer screening
  • smoking cessation
  • risk factors
  • squamous cell carcinoma
  • clinical trial
  • magnetic resonance
  • magnetic resonance imaging
  • young adults
  • alcohol consumption