Data from A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers
Authors: Chen Dan , Truong Therese , Gaborieau Valerie , Byrnes Graham , Chabrier Amelie , Chuang Shu-chun , Olshan Andrew F. , Weissler Mark C. , 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. , Lubiński 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 , Holcátová Ivana , Richiardi Lorenzo , Kjaerheim Kristina , Agudo Antonio , Castellsagué 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 , Wünsch-Filho Victor , Eluf-Neto José , Fernandez Leticia , Boccia Stefania , Hashibe Mia , Hayes Richard B. , Boffetta Paolo , Brennan Paul , McKay James D. 
Published: March 2023

<div>Abstract<p><b>Background:</b> 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, <i>P</i> = 0.003) with little effect in men (OR = 1.04, <i>P</i> = 0.35).</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, <i>P</i> = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, <i>P</i> = 0.66; <i>P</i>-heterogeneity (<i>P</i><sub>het</sub>) = 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, <i>P</i> = 7 × 10<sup>−6</sup>) but not males (OR = 1.02, 95% CI = 0.97–1.08, <i>P</i> = 0.35; <i>P</i><sub>het</sub> = 6 × 10<sup>−4</sup>). There was little evidence for a sex</p><p>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 (<i>P</i><sub>het</sub> = 0.86).</p><p><b>Conclusions:</b> This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers.</p><p><b>Impact:</b> Further research is warranted to elucidate the mechanisms underlying these observations. <i>Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.</i></p></div>