Abstract

BACKGROUND: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. METHODS: ) and diabetes (duration =3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency =0.005, genotyped in at least one dataset) were analyzed. Case-control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. RESULTS: ). CONCLUSIONS: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. IMPACT: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer.

Authors	Tang, Hongwei; Jiang, Lai; Stolzenberg-Solomon, Rachael Z; 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, Loïc; Neale, Rachel E; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Zheng, Wei; Albanes, Demetrius; Andreotti, Gabriella; Babic, Ana; Bamlet, William R; Berndt, Sonja I; Blackford, Amanda; Bueno-de-Mesquita, Bas; Buring, Julie E; Campa, Daniele; Chanock, Stephen J; Childs, Erica; Duell, Eric J; Fuchs, Charles; Gaziano, J Michael; Goggins, Michael; Hartge, Patricia; Hassam, Manal H; Holly, Elizabeth A; Hoover, Robert N; Hung, Rayjean J; Kurtz, Robert C; Lee, I-Min; Malats, Núria; Milne, Roger L; Ng, Kimmie; Oberg, Ann L; Orlow, Irene; Peters, Ulrike; Porta, Miquel; Rabe, Kari G; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Silverman, Debra T; Thompson, Ian M; Tjønneland, Anne; Trichopoulou, Antonia; Wactawski-Wende, Jean; Wentzensen, Nicolas; Wilkens, Lynne R; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Amundadottir, Laufey T; Jacobs, Eric J; Petersen, Gloria M; Wolpin, Brian M; Risch, Harvey A; Chatterjee, Nilanjan; Klein, Alison P; Li, Donghui; Kraft, Peter; Wei, Peng
Journal	Cancer Epidemiology Biomarkers and Prevention
Pages	1784-1791
Volume	29
Date	1/06/2020
Grant ID	U01 CA182934
Funding Body	NCI NIH HHS
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/1055-9965.EPI-20-0275