A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Dan Chen, Therese Truong, Valerie Gaborieau, Graham Byrnes, Amelie Chabrier, Shu-Chun Chuang, Andrew F. Olshan, Mark C. Weissler, Jingchun Luo, Marjorie Romkes, Shama Buch, Tomoko Nukui, Silvia Franceschi, Rolando Herrero, Renato Talamini, Karl T. Kelsey, Brock Christensen, Michael D. McClean, Martin Lacko, Johannes J. ManniWilbert H. M. Peters, Jan Lubinski, Joanna Trubicka, Marcin Lener, Joshua E. Muscat, Philip Lazarus, Qingyi Wei, Erich M. Sturgis, Zuo-Feng Zhang, Shen-Chih Chang, Renyi Wang, Stephen M. Schwartz, Chu Chen, Simone Benhamou, Pagona Lagiou, Ivana Holcatov, Lorenzo Richiardi, Kristina Kjaerheim, Antonio Agudo, Xavier Castellsague, Tatiana V. Macfarlane, Luigi Barzan, Cristina Canova, Nalin S. Thakker, David I. Conway, Ariana Znaor, Claire M. Healy, Wolfgang Ahrens, David Zaridze, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Eleonora Fabianova, Alexandru Bucur, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Maria Paula Curado, Sergio Koifman, Ana M. Menezes, Victor Wuensch-Filho, Jose Eluf-Neto, Leticia Fernandez, Stefania Boccia, Mia Hashibe, Richard B. Hayes, Paolo Boffetta, Paul Brennan, James D. Mckay*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)


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 (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 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: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P-het) = 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 (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P-het = 6 x 10(-4)). 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 (P-het = 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.
Original languageEnglish
Pages (from-to)658-664
JournalCancer Epidemiology Biomarkers & Prevention
Issue number4
Publication statusPublished - Apr 2011

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