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Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Authors :
Mocci, Evelina
Kundu, Prosenjit
Wheeler, William
Arslan, Alan A.
Beane-Freeman, Laura E.
Bracci, Paige M.
Brennan, Paul
Canzian, Federico
Du, Mengmeng
Gallinger, Steven
Giles, Graham G.
Goodman, Phyllis J.
Kooperberg, Charles
Le Marchand, Loic
Neale, Rachel E.
Shu, Xiao-Ou
Visvanathan, Kala
White, Emily
Zheng, Wei
Albanes, Demetrius
Andreotti, Gabriella
Babic, Ana
Bamlet, William R.
Berndt, Sonja
Blackford, Amanda L.
Bueno-de-Mesquita, Bas
Buring, Julie E.
Campa, Daniele
Chanock, Stephen J.
Childs, Erica J.
Duell, Eric J.
Fuchs, Charles S.
Gaziano, J. Michael
Giovannucci, Edward L.
Goggins, Michael G.
Hartge, Patricia
Hassan, Manal M.
Holly, Elizabeth A.
Hoover, Robert N.
Hung, Rayjean J.
Kurtz, Robert C.
Lee, I-Min
Malats, Nuria
Milne, Roger L.
Ng, Kimmie
Oberg, Ann L.
Panico, Salvatore
Peters, Ulrike
Porta, Miquel
Rabe, Kari G.
Riboli, Elio
Rothman, Nathaniel
Scelo, Ghislaine
Sesso, Howard D.
Silverman, Debra T.
Stevens, Victoria L.
Strobel, Oliver
Thompson, Ian M.
Tjonneland, Anne
Trichopoulou, Antonia
Van den Eeden, Stephen K.
Wactawski-Wende, Jean
Wentzensen, Nicolas
Wilkens, Lynne R.
Yu, Herbert
Yuan, Fangcheng
Zeleniuch-Jacquotte, Anne
Amundadottir, Laufey T.
Li, Donghui
Jacobs, Eric J.
Petersen, Gloria M.
Wolpin, Brian M.
Risch, Harvey A.
Kraft, Peter
Chatterjee, Nilanjan
Klein, Alison P.
Stolzenberg-Solomon, Rachael
Mocci, Evelina
Kundu, Prosenjit
Wheeler, William
Arslan, Alan A.
Beane-Freeman, Laura E.
Bracci, Paige M.
Brennan, Paul
Canzian, Federico
Du, Mengmeng
Gallinger, Steven
Giles, Graham G.
Goodman, Phyllis J.
Kooperberg, Charles
Le Marchand, Loic
Neale, Rachel E.
Shu, Xiao-Ou
Visvanathan, Kala
White, Emily
Zheng, Wei
Albanes, Demetrius
Andreotti, Gabriella
Babic, Ana
Bamlet, William R.
Berndt, Sonja
Blackford, Amanda L.
Bueno-de-Mesquita, Bas
Buring, Julie E.
Campa, Daniele
Chanock, Stephen J.
Childs, Erica J.
Duell, Eric J.
Fuchs, Charles S.
Gaziano, J. Michael
Giovannucci, Edward L.
Goggins, Michael G.
Hartge, Patricia
Hassan, Manal M.
Holly, Elizabeth A.
Hoover, Robert N.
Hung, Rayjean J.
Kurtz, Robert C.
Lee, I-Min
Malats, Nuria
Milne, Roger L.
Ng, Kimmie
Oberg, Ann L.
Panico, Salvatore
Peters, Ulrike
Porta, Miquel
Rabe, Kari G.
Riboli, Elio
Rothman, Nathaniel
Scelo, Ghislaine
Sesso, Howard D.
Silverman, Debra T.
Stevens, Victoria L.
Strobel, Oliver
Thompson, Ian M.
Tjonneland, Anne
Trichopoulou, Antonia
Van den Eeden, Stephen K.
Wactawski-Wende, Jean
Wentzensen, Nicolas
Wilkens, Lynne R.
Yu, Herbert
Yuan, Fangcheng
Zeleniuch-Jacquotte, Anne
Amundadottir, Laufey T.
Li, Donghui
Jacobs, Eric J.
Petersen, Gloria M.
Wolpin, Brian M.
Risch, Harvey A.
Kraft, Peter
Chatterjee, Nilanjan
Klein, Alison P.
Stolzenberg-Solomon, Rachael
Source :
Mocci , E , Kundu , P , Wheeler , W , Arslan , A A , Beane-Freeman , L E , Bracci , P M , Brennan , P , Canzian , F , Du , M , Gallinger , S , Giles , G G , Goodman , P J , Kooperberg , C , Le Marchand , L , Neale , R E , Shu , X-O , Visvanathan , K , White , E , Zheng , W , Albanes , D , Andreotti , G , Babic , A , Bamlet , W R , Berndt , S , Blackford , A L , Bueno-de-Mesquita , B , Buring , J E , Campa , D , Chanock , S J , Childs , E J , Duell , E J , Fuchs , C S , Gaziano , J M , Giovannucci , E L , Goggins , M G , Hartge , P , Hassan , M M , Holly , E A , Hoover , R N , Hung , R J , Kurtz , R C , Lee , I-M , Malats , N , Milne , R L , Ng , K , Oberg , A L , Panico , S , Peters , U , Porta , M , Rabe , K G , Riboli , E , Rothman , N , Scelo , G , Sesso , H D , Silverman , D T , Stevens , V L , Strobel , O , Thompson , I M , Tjonneland , A , Trichopoulou , A , Van den Eeden , S K , Wactawski-Wende , J , Wentzensen , N , Wilkens , L R , Yu , H , Yuan , F , Zeleniuch-Jacquotte , A , Amundadottir , L T , Li , D , Jacobs , E J , Petersen , G M , Wolpin , B M , Risch , H A , Kraft , P , Chatterjee , N , Klein , A P & Stolzenberg-Solomon , R 2021 , ' Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3 ' , Cancer Research , vol. 81 , no. 11 , pp. 3134-3143 .
Publication Year :
2021

Abstract

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 similar to 10(-8) was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P-interaction = 3.08 x 10(-9)). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r(2) = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.Significance: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.

Details

Database :
OAIster
Journal :
Mocci , E , Kundu , P , Wheeler , W , Arslan , A A , Beane-Freeman , L E , Bracci , P M , Brennan , P , Canzian , F , Du , M , Gallinger , S , Giles , G G , Goodman , P J , Kooperberg , C , Le Marchand , L , Neale , R E , Shu , X-O , Visvanathan , K , White , E , Zheng , W , Albanes , D , Andreotti , G , Babic , A , Bamlet , W R , Berndt , S , Blackford , A L , Bueno-de-Mesquita , B , Buring , J E , Campa , D , Chanock , S J , Childs , E J , Duell , E J , Fuchs , C S , Gaziano , J M , Giovannucci , E L , Goggins , M G , Hartge , P , Hassan , M M , Holly , E A , Hoover , R N , Hung , R J , Kurtz , R C , Lee , I-M , Malats , N , Milne , R L , Ng , K , Oberg , A L , Panico , S , Peters , U , Porta , M , Rabe , K G , Riboli , E , Rothman , N , Scelo , G , Sesso , H D , Silverman , D T , Stevens , V L , Strobel , O , Thompson , I M , Tjonneland , A , Trichopoulou , A , Van den Eeden , S K , Wactawski-Wende , J , Wentzensen , N , Wilkens , L R , Yu , H , Yuan , F , Zeleniuch-Jacquotte , A , Amundadottir , L T , Li , D , Jacobs , E J , Petersen , G M , Wolpin , B M , Risch , H A , Kraft , P , Chatterjee , N , Klein , A P & Stolzenberg-Solomon , R 2021 , ' Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3 ' , Cancer Research , vol. 81 , no. 11 , pp. 3134-3143 .
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322762618
Document Type :
Electronic Resource