dc.contributor.author | Li, Donghui | |
dc.contributor.author | Duell, Eric J. | |
dc.contributor.author | Yu, Kai | |
dc.contributor.author | Risch, Harvey A. | |
dc.contributor.author | Olson, Sara H. | |
dc.contributor.author | Kooperberg, Charles | |
dc.contributor.author | Wolpin, Brian M. | |
dc.contributor.author | Jiao, Li | |
dc.contributor.author | Dong, Xiaoqun | |
dc.contributor.author | Wheeler, Bill | |
dc.contributor.author | Arslan, Alan A. | |
dc.contributor.author | Bueno-de-Mesquita, H. Bas | |
dc.contributor.author | Fuchs, Charles S. | |
dc.contributor.author | Gallinger, Steven | |
dc.contributor.author | Gross, Myron | |
dc.contributor.author | Hartge, Patricia | |
dc.contributor.author | Hoover, Robert N. | |
dc.contributor.author | Holly, Elizabeth A. | |
dc.contributor.author | Jacobs, Eric J. | |
dc.contributor.author | Klein, Alison P. | |
dc.contributor.author | LaCroix, Andrea | |
dc.contributor.author | Mandelson, Margaret T. | |
dc.contributor.author | Petersen, Gloria | |
dc.contributor.author | Zheng, Wei | |
dc.contributor.author | Agalliu, Ilir | |
dc.contributor.author | Albanes, Demetrius | |
dc.contributor.author | Boutron-Ruault, Marie-Christine | |
dc.contributor.author | Bracci, Paige M. | |
dc.contributor.author | Buring, Julie E. | |
dc.contributor.author | Canzian, Federico | |
dc.contributor.author | Chang, Kenneth | |
dc.contributor.author | Chanock, Stephen J. | |
dc.contributor.author | Cotterchio, Michelle | |
dc.contributor.author | Gaziano, J.Michael | |
dc.contributor.author | Giovannucci, Edward L. | |
dc.contributor.author | Goggins, Michael | |
dc.contributor.author | Hallmans, Göran | |
dc.contributor.author | Hankinson, Susan E. | |
dc.contributor.author | Bolton, Judith Hoffman | |
dc.contributor.author | Hunter, David J. | |
dc.contributor.author | Hutchinson, Amy | |
dc.contributor.author | Jacobs, Kevin B. | |
dc.contributor.author | Jenab, Mazda | |
dc.contributor.author | Khaw, Kay-Tee | |
dc.contributor.author | Kraft, Peter | |
dc.contributor.author | Krogh, Vittorio | |
dc.contributor.author | Kurtz, Robert C. | |
dc.contributor.author | McWilliams, Robert R. | |
dc.contributor.author | Mendelsohn, Julie B. | |
dc.contributor.author | Patel, Alpa V. | |
dc.contributor.author | Rabe, Kari G. | |
dc.contributor.author | Riboli, Elio | |
dc.contributor.author | Shu, Xiao-Ou | |
dc.contributor.author | Tjønneland, Anne | |
dc.contributor.author | Tobias, Geoffrey S. | |
dc.contributor.author | Trichopoulos, Dimitrios | |
dc.contributor.author | Virtamo, Jarmo | |
dc.contributor.author | Visvanathan, Kala | |
dc.contributor.author | Watters, Joanne | |
dc.contributor.author | Yu, Herbert | |
dc.contributor.author | Zeleniuch-Jacquotte, Anne | |
dc.contributor.author | Amundadottir, Laufey | |
dc.contributor.author | Stolzenberg-Solomon, Rachael Z. | |
dc.date.accessioned | 2019-09-23T15:35:14Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Li, Donghui, Eric J. Duell, Kai Yu, Harvey A. Risch, Sara H. Olson, Charles Kooperberg, Brian M. Wolpin, et al. 2012. “Pathway Analysis of Genome-Wide Association Study Data Highlights Pancreatic Development Genes as Susceptibility Factors for Pancreatic Cancer.” Carcinogenesis 33 (7): 1384–90. https://doi.org/10.1093/carcin/bgs151. | |
dc.identifier.issn | 0143-3334 | |
dc.identifier.issn | 1460-2180 | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41392169 | * |
dc.description.abstract | Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 x 10(-6), 1.6 x 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 x 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. | |
dc.language.iso | en_US | |
dc.publisher | Oxford University Press | |
dash.license | META_ONLY | |
dc.title | Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | Carcinogenesis | |
dash.depositing.author | Giovannucci, Edward L.::fd8dcb59a5a5859f2a85fabae12a60cf::600 | |
dc.date.available | 2019-09-23T15:35:14Z | |
dash.workflow.comments | 1Science Serial ID 26815 | |
dc.identifier.doi | 10.1093/carcin/bgs151 | |
dash.source.volume | 33;7 | |
dash.source.page | 1384 | |