Upper Aerodigestive Tract Cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR1⁄4 1.24, P1⁄4 0.003) with little effect in men (OR 1⁄4 1.04, P 1⁄4 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies. Results: rs16969968was again associatedwithUADT cancers inwomen (OR1⁄4 1.21, 95%CI1⁄4 1.08–1.36, P1⁄4 0.001) and a similar lack of observed effect in men [OR 1⁄4 1.02, 95% CI 1⁄4 0.95–1.09, P 1⁄4 0.66; P-heterogeneity (Phet) 1⁄4 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR1⁄4 1.22, 95%CI1⁄4 1.12–1.34, P1⁄4 7 10 ) but not males (OR 1⁄4 1.02, 95% CI 1⁄4 0.97–1.08, P 1⁄4 0.35; Phet 1⁄4 6 10 ). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet 1⁄4 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. 2011 AACR. Authors' Affiliations: International Agency for Research on Cancer (IARC), Lyon, France; Gillings School of Global Public Health; School of Medicine; Otolaryngology/Head and Neck Surgery; and Lineberger Comprehensive Cancer Site, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; University of Pittsburgh, Pittsburgh, Pennsylvania; Instituto de Investigaci on Epidemiol ogica, San Jos e, Costa Rica; National Cancer Institute, IRCSS, Aviano, Italy; Brown University, Providence, Rhode Island; Boston University School of Public Health, Boston, Massachusetts; Department of Otorhinolaryngology and Head and Neck Surgery, Maastricht University Medical Site, Maastricht; and Department of Gastroenterology, Radboud University Nijmegen Medical Site, Nijmegen, the Netherlands; Pomeranian Medical University, Department of Genetics and Pathomorphology, International Hereditary Cancer Site, Szczecin, Poland; Penn State College of Medicine, Hershey, Pennsylvania; University of Texas MD Anderson Cancer Site, Houston, Texas; University of California, Los Angeles, School of Public Health, Los Angeles, California; Fred Hutchinson Cancer Research Site, Seattle, Washington; INSERM U946, Paris; CNRS UMR8200, Gustave Roussy Institute, Villejuif, France; University of Athens School of Medicine, Athens, Greece; Institute of Hygiene and Epidemiology,1st Faculty of Medicine, Charles University in Prague, Czech Republic; Unit of Cancer Epidemiology, University of Turin, Turin, Italy; Cancer Registry of Norway, Oslo, Norway; Institut Catal a d’Oncologia (ICO), Barcelona; and Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiologia y Salud Publica CIBERESP), Spain; School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom; General Hospital of Pordenone, Pordenone; Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy; MRC-HPA Centre for Environment and Health, Department of Respiratory Epidemiology and Public Health, D, Imperial College School of Medicine (NHLI), London and; University of Manchester, School of Dentistry, Manchester, United Kingdom; University of Glasgow Dental School, Glasgow, Scotland; Croatian National Cancer Registry, Croatian National Institute of Public Cancer Epidemiology, Biomarkers & Prevention Cancer Epidemiol Biomarkers Prev; 20(4) April 2011 658 American Association for Cancer Research Copyright © 2011 on June 4, 2012 cebp.aacrjournals.org Downloaded from Published OnlineFirst February 18, 2011; DOI:10.1158/1055-9965.EPI-10-1008