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Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis
R. Pastorino, A. Puggina, R. Carreras-Torres, P. Lagiou, I. Holcátová, L. Richiardi, K. Kjaerheim, A. Agudo, X. Castellsagué, TV. Macfarlane, L. Barzan, C. Canova, NS. Thakker, DI. Conway, A. Znaor, CM. Healy, W. Ahrens, D. Zaridze, N....
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- Genome-Wide Association Study MeSH
- Genetic Predisposition to Disease MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Mendelian Randomization Analysis methods MeSH
- Head and Neck Neoplasms genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Body Height genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.
Cancer Epidemiology Research Program Catalan Institute of Oncology Barcelona Spain
Cancer Registry of Norway Oslo Norway
Croatian National Cancer Registry Croatian National Institute of Public Health Zagreb Croatia
Department of Epidemiology Institute of Occupational Medicine Lodz Poland
General Hospital of Pordenone Pordenone Italy
Institute of Carcinogenesis Cancer Research Centre Moscow Russian Federation
International Agency for Research on Cancer Lyon France
Palacky University Olomouc Czech Republic
Regional Authority of Public Health Banska Bystrica Slovakia
School of Medicine and Dentistry University of Aberdeen Aberdeen United Kingdom
Trinity College School of Dental Science Dublin Ireland
University of Glasgow Dental School Glasgow Scotland United Kingdom
University of Manchester School of Dentistry Manchester United Kingdom
University of Turin Department of Medical Sciences Unit of Cancer Epidemiology Turin Italy
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