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Int J Cancer. 2015 Jul 15;137(2):448-62. doi: 10.1002/ijc.29388. Epub 2015 Jan 28.

Natural vitamin C intake and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Author information

  • 1Dipartimento di Scienze Cliche e di Comunità Sezione Di Statistica Medica E Biometria "Giulio A. Maccacaro,", Università degli Studi di Milano, Milan, Italy.
  • 2Division of Public Health, Department of Family and Preventive Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, USA.
  • 3Institute of Hygiene and Epidemiology, Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
  • 4Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri,", Milan, Italy.
  • 5S.C., Statistica Medica, Biometria e Bioinformatica, Fondazione IRCSS Istituto Nazionale Tumori di Milano, Milan, Italy.
  • 6Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano, Italy.
  • 7Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Kyushu, Japan.
  • 8Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
  • 9Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • 10Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD.
  • 11Department of Cancer Prevention and Control and Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY.
  • 12Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA.
  • 13Department of Epidemiology and Environmental Health Sciences, School of Public Health and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
  • 14Cancer Epidemiology Unit, Institute for Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
  • 15Department of Pathology and Laboratory Medicine and Department of Epidemiology, Brown University, Providence, RI.
  • 16Department of Environmental Health, Boston University School of Public Health, Boston, MA.
  • 17Department of Otolaryngology, New York Eye and Ear Infirmary, New York, NY.
  • 18Medical Informatics Center, Peking University, Peking, China.
  • 19 Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.
  • 20Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, UT.
  • 21Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.


Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40-0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.

© 2014 UICC.


INHANCE; head and neck cancer; laryngeal cancer; oral and pharyngeal cancer; vitamin C

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