- Li, Donghui
- Duell, Eric J
- Yu, Kai
- Risch, Harvey A
- Olson, Sara H
- Kooperberg, Charles
- Wolpin, Brian M
- Jiao, Li
- Dong, Xiaoqun
- Wheeler, Bill
- Arslan, Alan A
- Bueno-de-Mesquita, H Bas
- Fuchs, Charles S
- Gallinger, Steven
- Gross, Myron
- Hartge, Patricia
- Hoover, Robert N
- Holly, Elizabeth A
- Jacobs, Eric J
- Klein, Alison P
- LaCroix, Andrea
- Mandelson, Margaret T
- Petersen, Gloria
- Zheng, Wei
- Agalliu, Ilir
- Albanes, Demetrius
- Boutron-Ruault, Marie-Christine
- Bracci, Paige M
- Buring, Julie E
- Canzian, Federico
- Chang, Kenneth
- Chanock, Stephen J
- Cotterchio, Michelle
- Gaziano, J Michael
- Giovannucci, Edward L
- Goggins, Michael
- Hallmans, Göran
- Hankinson, Susan E
- Hoffman Bolton, Judith A
- Hunter, David J
- Hutchinson, Amy
- Jacobs, Kevin B
- Jenab, Mazda
- Khaw, Kay-Tee
- Kraft, Peter
- Krogh, Vittorio
- Kurtz, Robert C
- McWilliams, Robert R
- Mendelsohn, Julie B
- Patel, Alpa V
- Rabe, Kari G
- Riboli, Elio
- Shu, Xiao-Ou
- Tjønneland, Anne
- Tobias, Geoffrey S
- Trichopoulos, Dimitrios
- Virtamo, Jarmo
- Visvanathan, Kala
- Watters, Joanne
- Yu, Herbert
- Zeleniuch-Jacquotte, Anne
- Amundadottir, Laufey
- Stolzenberg-Solomon, Rachael Z
- et al.
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 × 10(-6), 1.6 × 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 × 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.