Citations 5
Physical activity and the risk of non‐Hodgkin lymphoma subtypes: A pooled analysis
Boyle, Terry , Kleinstern, Geffen , Bracci, Paige M. , Cerhan, James R. , Benavente, Yolanda , Casabonne, Delphine , Holly, Elizabeth A., Liebow, Mark , Paltiel, Ora , Robinson, Dennis P. , Rothman, Nathaniel , Wang, Sophia , Weisenburger, Dennis D. , Spinelli, John J., Norman, Aaron, Paltiel, Ora , Robinson, Dennis, Rothman, Nathaniel , Cerhan, James R , Wang, Sophia S , Chiu, Brian C.‐H. , Habermann, Thomas M. , Norman, Aaron D. , Rothman, Nathaniel , Seir, Rania Abu , Slager, Susan L. , Villeneuve, Paul J.
International Journal of Cancer | August 27, 2022 | Volume: 152 | Issue: 3 | Pages: 396-407
AbstractNon‐Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case‐control studies to examine the association between moderate‐to‐vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B‐cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T‐cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study‐specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case‐control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.
A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
Zhong, Jun, Jermusyk, Ashley , Wu, Lang , Hoskins, Jason W. , Collins, Irene , Mocci, Evelina , Song, Lei , Chung, Charles C., Xiao, Wenming , Andreotti, Gabriella , Arslan, Alan A. , Babić, Ana , Berndt, Sonja, Borgida, Ayelet , Bracci, Paige M. , Brennan, Paul , Bueno‐de‐Mesquita, Bas , Buring, Julie E. , Childs, Erica J., Du, Mengmeng , Fuchs, Charles S. , Gallinger, Steven , Gaziano, J. Michael, Giovannucci, Edward L. , Goodman, Gary E. , Goodman, Phyllis J. , Haiman, Christopher, Hartge, Patricia, Hasan, Manal , Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A. , Kogevinas, Manolis, Kurtz, Robert J., Ng, Kimmie , Obazee, Ofure , Oberg, Ann L. , Patel, Alpa V. , Peters, Ulrike , Porta, Miquel , Rothman, Nathaniel , Scélo, Ghislaine , Sesso, Howard D. , Sieri, Sabina , Tjønneland, Anne , Thornquist, Mark, Trichopoulou, Antonia , Visvanathan, Kala , Wactawski‐Wende, Jean , Wentzensen, Nicolas , Yuan, Chen , Zeleniuch‐Jacquotte, Anne , Hoover, Robert N. , Brown, Kevin M. , Jacobs, Eric J. , Li, Donghui , Yu, Kai , Wolpin, Brian M. , Chatterjee, Nilanjan , Shi, Jianxin , Petersen, Gloria M. , Zhong, Jun , Arslan, Alan A , Tjønneland, Anne , Wactawski-Wende, Jean , Visvanathan, Kala , Klein, Eric A , Porta, Miquel , Zeleniuch-Jacquotte, Anne , Zhong, Jun , Yuan, Chen , Hoskins, Jason W , Zhang, Mingfeng , Zhang, Tongwu , Albanes, Demetrius , Bamlet, William R. , Freeman, Laura E. Beane , Brais, Lauren K , Canzian, Federico , Cotterchio, Michelle , Duell, Eric J. , Giles, Graham G. , Goggins, Michael , Marchand, Loı̈c Le , Malats, Núria , Männistö, Satu , Milne, Roger L. , Neale, Rachel Ε. , Orlow, Irene , Rothman, Nathaniel , Severi, Gianluca , Silverman, Debra T. , Sund, Malin , Tobias, Geoffrey S. , Van Den Eeden, Stephen K , White, Emily , Yu, Kai , Kooperberg, Charles , Risch, Harvey A. , Shu, Xiao‐Ou , Chanock, Stephen Jacob , Stolzenberg‐Solomon, Rachael Z. , Klein, Alison P. , Smith, Jill Palmer , Kraft, Peter , Zheng, Wei , Ámundadóttir, Laufey T.
JNCI: Journal of the National Cancer Institute | December 31, 2019 | Volume: 112 | Issue: 10 | Pages: 1003-1012
Abstract Background Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74–421 samples). Results We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
Walsh, Naomi , Hyland, Paula L. , Yang, Qi , Childs, Erica J., Collins, Irene , Wang, Zhaoming , Arslan, Alan A. , Bracci, Paige M. , Brennan, Paul , Canzian, Federico , Gallinger, Steven , Goodman, Gary E. , Goodman, Phyllis J. , Hung, Rayjean J, Kurtz, Robert C. , Scélo, Ghislaine , Shu, Xiao Ou , Visvanathan, Kala , consortia, PanScan and PanC4, Andreotti, Gabriella , Babić, Ana , Berndt, Sonja I. , Borgida, Ayelet , Bueno‐de‐Mesquita, Bas , Buring, Julie E. , Chaffee, Kari G. , Foretová, Lenka , Fuchs, Charles S. , Gaziano, J. Michael , Giovannucci, Edward, Hackert, Thilo , Haiman, Christopher A. , Hartge, Patricia, Hasan, Manal , Helzlsouer, Kathy J., Herman, Joseph M. , Holly, Elizabeth A., Hoover, Robert N. , Hung, Rayjean J, Janout, Vladimír , Klein, Eric A. , Laheru, Daniel A. , Lee, I‐Min , Oberg, Ann L. , Patel, Alpa V. , Peters, Ulrike , Porta, Miquel , Real, Francisco X. , Rothman, Nathaniel , Sesso, Howard D. , Strobel, Oliver , Thornquist, Mark, Wactawski‐Wende, Jean , Wareham, Nick, Weiderpass, Elisabete , Wentzensen, Nicolas , Wheeler, William, Zeleniuch‐Jacquotte, Anne , Kraft, Peter , Li, Donghui , Jacobs, Eric J. , Petersen, Gloria M. , Wolpin, Brian M. , Rabe, Kari G. , Hung, Rayjean J. , Cleary, Sean, Weiderpass, Elisabete , Arslan, Alan A , Canzian, Federico , Hung, Rayjean J , Wactawski-Wende, Jean , Wang, Zhaoming , Visvanathan, Kala , Klein, Eric A , Strobel, Oliver , Kraft, Peter , Porta, Miquel , Real, Francisco X , Zeleniuch-Jacquotte, Anne , Zhang, Han , Mocci, Evelina , Zhang, Mingfeng , Freeman, Laura E. Beane , Duell, Eric J. , Giles, Graham G. , Goggins, Michael , Hung, Rayjean J, Kooperberg, Charles , Malats, Núria , Marchand, Loı̈c Le , Neale, Rachel Ε. , Olson, Sara H. , Van Den Eeden, Stephen K , White, Emily , Zheng, Wei , consortia, PanScan and PanC4, Albanes, Demetrius , Bamlet, William R. , Boutron‐Ruault, Marie‐Christine , Brais, Lauren K , Chanock, Stephen Jacob , Cleary, Sean P. , Cotterchio, Michelle , Holcátová, Ivana , Hung, Rayjean J, Lu, Lingeng , Männistö, Satu , Milne, Roger L. , Orlow, Irene , Rothman, Nathaniel , Severi, Gianluca , Silverman, Debra T. , Sund, Malin , Tobias, Geoffrey S. , Wareham, Nick, Yu, Kai , Risch, Harvey A. , Ámundadóttir, Laufey T. , Yu, Kai , Klein, Alison P. , Stolzenberg‐Solomon, Rachael Z.
JNCI: Journal of the National Cancer Institute | August 15, 2018 | Volume: 111 | Issue: 6 | Pages: 557-567
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Wang, Sophia , Carrington, Mary , Berndt, Sonja I. , Bracci, Paige M. , Smedby, Karin E. , Hjalgrim, Henrik , Vijai, Joseph , Morton, Lindsay M. , Vermeulen, Roel , Paltiel, Ora , Vajdic, Claire M. , Linet, Martha S. , Nieters, Alexandra , Sanjosé, Sílvia de, Brown, Elizabeth E. , Turner, Jennifer , Spinelli, John J., Zheng, Tongzhang, Birmann, Brenda M. , Flowers, Christopher R. , Becker, Nikolaus, Holly, Elizabeth A., Kane, Eleanor , Weisenburger, Dennis D. , Cocco, Pierluigi, Weinstein, Stephanie J. , Diver, W. Ryan , Lax, S. , Travis, Ruth C., Kaaks, Rudolph, Ríboli, Elio , Benavente, Yolanda , Brennan, Paul, McKay, James , Delfau‐Larue, Marie‐Hélène , Link, Brian K. , Magnani, Corrado , Latte, Giancarlo, Doo, Nicole Wong , Offit, Kenneth , Musinsky, Jacob, Arslan, Alan A. , Purdue, Mark P. , Adami, Hans‐Olov , Melbye, Mads , Glimelius, Bengt , Conde, Lucía , Camp, Nicola J. , Glenn, Martha, Curtin, Karen , Clavel, Jacqueline , Monnereau, Alain, Cox, David G. , Ghesquières, Hervé , Salles, Gilles , Bofetta, Paulo, Foretová, Lenka , Staines, Anthony , Davis, S. Scott , Severson, Richard K., Lan, Qing , Brooks‐Wilson, Angela , Smith, Martyn T. , Roman, Eve , Kricker, Anne , Zhang, Yawei , Kraft, Peter , Rothman, Nathaniel , Hartge, Patricia, Skibola, Christine F., Cocco, Pierluigi , Travis, Ruth C. , Monnereau, Alain , Turner, Jennifer , Weinstein, Stephanie J , Link, Brian K , Joseph, Vijai , Cocco, Pierluigi , Brooks-Wilson, Angela R , Vajdic, Claire M , Kane, Eleanor , Arslan, Alan A , Travis, Ruth C , Kraft, Peter , Morton, Lindsay M , Salles, Gilles A , Wang, Sophia S , Birmann, Brenda M , Roman, Eve , Clavel, Jacqueline , Riboli, Elio , Slager, Susan L. , Voutsinas, Jenna M. , Cerhan, James R. , Cozen, Wendy , Maynadié, Marc , Albanes, Demetrius , Teras, Lauren R. , Ennas, Maria Grazia , Feldman, Andrew L. , Giles, Graham G. , Southey, Melissa C. , Milne, Roger L. , Chanock, Stephen Jacob , Doo, Nicole Wong
Cancer Research | May 7, 2018 | Volume: 78 | Issue: 14 | Pages: 4086-4096
Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
Abstract 2214: Genome-wide gene-diabetes and gene-obesity interaction scan in the pancreatic cancer case control consortium
Tang, Hongwei, Bueno-de-Mesquita, H. Bas, Gallinger, Steven , Holly, Elizabeth A., Petersen, Gloria M. , Bracci, Paige M. , Ríboli, Elio , Trichopoulos, Dimitrios, Peeters, Petra H., Li, Donghui , Duell, Eric J. , Risch, Harvey A. , Olson, Sara H. , McWilliams, Robert R. , Jenab, Mazda , Tjønneland, Anne , Boutron‐Ruault, Marie‐Christine , Kaaks, Rudolf , Panico, Salvatore , Sund, Malin , Khaw, Kay‐Tee , Amos, Christopher I. , Wei, Peng , Riboli, Elio
Cancer Research | May 1, 2015 | Volume: 74 | Issue: 19_Supplement | Pages: 2214-2214
Abstract Introduction Pancreatic cancer is a highly lethal malignancy due to late diagnosis and aggressiveness of the tumor. Characterization of high-risk populations for monitoring, intervention and early detection remains challenging. Obesity and diabetes are potentially modifiable contributors to pancreatic cancer. Genetic factors modifying the risk of obesity- and diabetes-induced pancreatic cancer have previously not been fully investigated at the genome-wide level. Hypothesis There are potential genetic factors modifying the associations between obesity/diabetes and pancreatic cancer. Methods Integrating genotype with risk factor data from a GWAS for the Pancreatic Cancer Case Control Consortium, we performed a genome-wide gene-environment interaction (G x E) scan for 457,688 SNPs in a discovery study of 2,028 cases and 2,109 controls using state-of-the-art methods including case-only (CO), case-control (CC), Empirical Hierarchical Bayes (EHB), Empirical-Bayes test (EB) and three 2-step approaches (DG2, EG2, DGEG2). Results We detected a genome-wide significant (P < 1.09 x 10-7 ) interaction of diabetes with rs13061928 (in CNTN4) in CO (P = 8.8 x 10-8 ), which was independent of diabetes in control group (P = 0.08). The minor allele was in a synergism with diabetes on the cancer risk: diabetics carrying GA/AA genotype had a 3.39-fold (95% CI: 2.47-4.65) increased disease risk compared with non-diabetics carrying GG genotype. Consistently, the SNP-diabetes interaction had a high ranking statistic in EHB (No.1) and high p-value ranks for EG2 and DGEG2 methods (No.1, P= 5.44 x 10-5). Conclusions These observations, once validated/confirmed, may help define at-risk subpopulation and initiate targeted intervention and prevention of pancreatic cancer. Genome-wide G x E analysis requires larger sample size than genetic main effects scan; combining the CO method with alternative methods may be the optimal scheme for genome-wide G x E analysis. Citation Format: Hongwei Tang, Eric J. Duell, Harvey A. Risch Risch, Sara H. Olson, H. Bas Bueno-de-Mesquita, Steven Gallinger, Elizabeth A. Holly, Gloria M. Petersen, Paige M. Bracci, Robert R. McWilliams, Mazda Jenab, Elio Riboli, Anne Tjønneland, Marie Christine Boutron-Ruault, Rudolf Kaaks, Dimitrios Trichopoulos, Salvatore Panico, Malin Sund, Petra H. M Peeters, Kay-Tee Khaw, Christopher I Amos, Donghui Li, Peng Wei. Genome-wide gene-diabetes and gene-obesity interaction scan in the pancreatic cancer case control consortium. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2214. doi:10.1158/1538-7445.AM2014-2214