Li, DonghuiDuell, Eric J.Yu, KaiRisch, Harvey A.Olson, Sara H.Kooperberg, CharlesWolpin, Brian M.Jiao, LiDong, XiaoqunWheeler, BillArslan, Alan A.Bueno-de-Mesquita, H. BasFuchs, Charles S.Gallinger, StevenGross, MyronHartge, PatriciaHoover, Robert N.Holly, Elizabeth A.Jacobs, Eric J.Klein, Alison P.LaCroix, AndreaMandelson, Margaret T.Petersen, GloriaZheng, WeiAgalliu, IlirAlbanes, DemetriusBoutron-Ruault, Marie-ChristineBracci, Paige M.Buring, Julie E.Canzian, FedericoChang, KennethChanock, Stephen J.Cotterchio, MichelleGaziano, J.MichaelGiovannucci, Edward L.Goggins, MichaelHallmans, GöranHankinson, Susan E.Bolton, Judith HoffmanHunter, David J.Hutchinson, AmyJacobs, Kevin B.Jenab, MazdaKhaw, Kay-TeeKraft, PeterKrogh, VittorioKurtz, Robert C.McWilliams, Robert R.Mendelsohn, Julie B.Patel, Alpa V.Rabe, Kari G.Riboli, ElioShu, Xiao-OuTjønneland, AnneTobias, Geoffrey S.Trichopoulos, DimitriosVirtamo, JarmoVisvanathan, KalaWatters, JoanneYu, HerbertZeleniuch-Jacquotte, AnneAmundadottir, LaufeyStolzenberg-Solomon, Rachael Z.2019-09-232012Li, 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/bgs151.0143-33341460-2180http://nrs.harvard.edu/urn-3:HUL.InstRepos:41392169Four 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.en-USJournal Article2019-09-2310.1093/carcin/bgs151