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


Chen, Dan; Truong, Therese; Gaborieau, Valerie; Byrnes, Graham; Chabrier, Amelie; Chuang, Shu-Chun; Olshan, Andrew F.; Weissler, Mark Christian; Luo, Jingchun; & Romkes, Marjorie, et al. (2011). A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers. Cancer Epidemiology, Biomarkers & Prevention, 20(4), 658-664. PMCID: PMC3070066


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 (odds ratio (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% confidence interval(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=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=7x10-6) but not males (OR=1.02, 95%CI=0.97-1.08, P=0.35) (P-heterogeneity=6x10-4). 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-heterogeneity=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.


Reference Type

Journal Article

Year Published


Journal Title

Cancer Epidemiology, Biomarkers & Prevention


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