Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

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Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3. / 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.

In: Cancer Research, Vol. 81, No. 11, 2021, p. 3134-3143.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mocci, E, Kundu, P, Wheeler, W, Arslan, AA, Beane-Freeman, LE, Bracci, PM, Brennan, P, Canzian, F, Du, M, Gallinger, S, Giles, GG, Goodman, PJ, Kooperberg, C, Le Marchand, L, Neale, RE, Shu, X-O, Visvanathan, K, White, E, Zheng, W, Albanes, D, Andreotti, G, Babic, A, Bamlet, WR, Berndt, S, Blackford, AL, Bueno-de-Mesquita, B, Buring, JE, Campa, D, Chanock, SJ, Childs, EJ, Duell, EJ, Fuchs, CS, Gaziano, JM, Giovannucci, EL, Goggins, MG, Hartge, P, Hassan, MM, Holly, EA, Hoover, RN, Hung, RJ, Kurtz, RC, Lee, I-M, Malats, N, Milne, RL, Ng, K, Oberg, AL, Panico, S, Peters, U, Porta, M, Rabe, KG, Riboli, E, Rothman, N, Scelo, G, Sesso, HD, Silverman, DT, Stevens, VL, Strobel, O, Thompson, IM, Tjonneland, A, Trichopoulou, A, Van den Eeden, SK, Wactawski-Wende, J, Wentzensen, N, Wilkens, LR, Yu, H, Yuan, F, Zeleniuch-Jacquotte, A, Amundadottir, LT, Li, D, Jacobs, EJ, Petersen, GM, Wolpin, BM, Risch, HA, Kraft, P, Chatterjee, N, Klein, AP & Stolzenberg-Solomon, R 2021, 'Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3', Cancer Research, vol. 81, no. 11, pp. 3134-3143. https://doi.org/10.1158/0008-5472.CAN-20-3267

APA

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., ... Stolzenberg-Solomon, R. (2021). Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3. Cancer Research, 81(11), 3134-3143. https://doi.org/10.1158/0008-5472.CAN-20-3267

Vancouver

Mocci E, Kundu P, Wheeler W, Arslan AA, Beane-Freeman LE, Bracci PM et al. Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3. Cancer Research. 2021;81(11):3134-3143. https://doi.org/10.1158/0008-5472.CAN-20-3267

Author

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. / Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3. In: Cancer Research. 2021 ; Vol. 81, No. 11. pp. 3134-3143.

Bibtex

@article{fc5d17903d8042aa91f46e78ceb56b21,
title = "Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3",
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.",
keywords = "GENOME-WIDE ASSOCIATION, GENE-ENVIRONMENT INDEPENDENCE, ANTERIOR CINGULATE CORTEX, SUSCEPTIBILITY LOCI, CIGARETTE-SMOKING, METAANALYSIS, LINKAGE, PROTEIN, TRENDS, GWAS",
author = "Evelina Mocci and Prosenjit Kundu and William Wheeler and Arslan, {Alan A.} and Beane-Freeman, {Laura E.} and Bracci, {Paige M.} and Paul Brennan and Federico Canzian and Mengmeng Du and Steven Gallinger and Giles, {Graham G.} and Goodman, {Phyllis J.} and Charles Kooperberg and {Le Marchand}, Loic and Neale, {Rachel E.} and Xiao-Ou Shu and Kala Visvanathan and Emily White and Wei Zheng and Demetrius Albanes and Gabriella Andreotti and Ana Babic and Bamlet, {William R.} and Sonja Berndt and Blackford, {Amanda L.} and Bas Bueno-de-Mesquita and Buring, {Julie E.} and Daniele Campa and Chanock, {Stephen J.} and Childs, {Erica J.} and Duell, {Eric J.} and Fuchs, {Charles S.} and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Goggins, {Michael G.} and Patricia Hartge and Hassan, {Manal M.} and Holly, {Elizabeth A.} and Hoover, {Robert N.} and Hung, {Rayjean J.} and Kurtz, {Robert C.} and I-Min Lee and Nuria Malats and Milne, {Roger L.} and Kimmie Ng and Oberg, {Ann L.} and Salvatore Panico and Ulrike Peters and Miquel Porta and Rabe, {Kari G.} and Elio Riboli and Nathaniel Rothman and Ghislaine Scelo and Sesso, {Howard D.} and Silverman, {Debra T.} and Stevens, {Victoria L.} and Oliver Strobel and Thompson, {Ian M.} and Anne Tjonneland and Antonia Trichopoulou and {Van den Eeden}, {Stephen K.} and Jean Wactawski-Wende and Nicolas Wentzensen and Wilkens, {Lynne R.} and Herbert Yu and Fangcheng Yuan and Anne Zeleniuch-Jacquotte and Amundadottir, {Laufey T.} and Donghui Li and Jacobs, {Eric J.} and Petersen, {Gloria M.} and Wolpin, {Brian M.} and Risch, {Harvey A.} and Peter Kraft and Nilanjan Chatterjee and Klein, {Alison P.} and Rachael Stolzenberg-Solomon",
year = "2021",
doi = "10.1158/0008-5472.CAN-20-3267",
language = "English",
volume = "81",
pages = "3134--3143",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "11",

}

RIS

TY - JOUR

T1 - Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

AU - Mocci, Evelina

AU - Kundu, Prosenjit

AU - Wheeler, William

AU - Arslan, Alan A.

AU - Beane-Freeman, Laura E.

AU - Bracci, Paige M.

AU - Brennan, Paul

AU - Canzian, Federico

AU - Du, Mengmeng

AU - Gallinger, Steven

AU - Giles, Graham G.

AU - Goodman, Phyllis J.

AU - Kooperberg, Charles

AU - Le Marchand, Loic

AU - Neale, Rachel E.

AU - Shu, Xiao-Ou

AU - Visvanathan, Kala

AU - White, Emily

AU - Zheng, Wei

AU - Albanes, Demetrius

AU - Andreotti, Gabriella

AU - Babic, Ana

AU - Bamlet, William R.

AU - Berndt, Sonja

AU - Blackford, Amanda L.

AU - Bueno-de-Mesquita, Bas

AU - Buring, Julie E.

AU - Campa, Daniele

AU - Chanock, Stephen J.

AU - Childs, Erica J.

AU - Duell, Eric J.

AU - Fuchs, Charles S.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Goggins, Michael G.

AU - Hartge, Patricia

AU - Hassan, Manal M.

AU - Holly, Elizabeth A.

AU - Hoover, Robert N.

AU - Hung, Rayjean J.

AU - Kurtz, Robert C.

AU - Lee, I-Min

AU - Malats, Nuria

AU - Milne, Roger L.

AU - Ng, Kimmie

AU - Oberg, Ann L.

AU - Panico, Salvatore

AU - Peters, Ulrike

AU - Porta, Miquel

AU - Rabe, Kari G.

AU - Riboli, Elio

AU - Rothman, Nathaniel

AU - Scelo, Ghislaine

AU - Sesso, Howard D.

AU - Silverman, Debra T.

AU - Stevens, Victoria L.

AU - Strobel, Oliver

AU - Thompson, Ian M.

AU - Tjonneland, Anne

AU - Trichopoulou, Antonia

AU - Van den Eeden, Stephen K.

AU - Wactawski-Wende, Jean

AU - Wentzensen, Nicolas

AU - Wilkens, Lynne R.

AU - Yu, Herbert

AU - Yuan, Fangcheng

AU - Zeleniuch-Jacquotte, Anne

AU - Amundadottir, Laufey T.

AU - Li, Donghui

AU - Jacobs, Eric J.

AU - Petersen, Gloria M.

AU - Wolpin, Brian M.

AU - Risch, Harvey A.

AU - Kraft, Peter

AU - Chatterjee, Nilanjan

AU - Klein, Alison P.

AU - Stolzenberg-Solomon, Rachael

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - GENOME-WIDE ASSOCIATION

KW - GENE-ENVIRONMENT INDEPENDENCE

KW - ANTERIOR CINGULATE CORTEX

KW - SUSCEPTIBILITY LOCI

KW - CIGARETTE-SMOKING

KW - METAANALYSIS

KW - LINKAGE

KW - PROTEIN

KW - TRENDS

KW - GWAS

U2 - 10.1158/0008-5472.CAN-20-3267

DO - 10.1158/0008-5472.CAN-20-3267

M3 - Journal article

C2 - 33574088

VL - 81

SP - 3134

EP - 3143

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -

ID: 272399825