TY - JOUR
TI - Genome-wide gene⇓diabetes and gene⇓obesity interaction scan in 8,255 cases and 11,900 controls from panscan and PanC4 consortia
AU - Tang, H.
AU - Jiang, L.
AU - Stolzenberg-Solomon, R.Z.
AU - Arslan, A.A.
AU - Beane Freeman, L.E.
AU - Bracci, P.M.
AU - Brennan, P.
AU - Canzian, F.
AU - Du, M.
AU - Gallinger, S.
AU - Giles, G.G.
AU - Goodman, P.J.
AU - Kooperberg, C.
AU - Le Marchand, L.
AU - Neale, R.E.
AU - Shu, X.-O.
AU - Visvanathan, K.
AU - White, E.
AU - Zheng, W.
AU - Albanes, D.
AU - Andreotti, G.
AU - Babic, A.
AU - Bamlet, W.R.
AU - Berndt, S.I.
AU - Blackford, A.
AU - Bueno-De-Mesquita, B.
AU - Buring, J.E.
AU - Campa, D.
AU - Chanock, S.J.
AU - Childs, E.
AU - Duell, E.J.
AU - Fuchs, C.
AU - Michael Gaziano, J.
AU - Goggins, M.
AU - Hartge, P.
AU - Hassam, M.H.
AU - Holly, E.A.
AU - Hoover, R.N.
AU - Hung, R.J.
AU - Kurtz, R.C.
AU - Lee, I.-M.
AU - Malats, N.
AU - Milne, R.L.
AU - Ng, K.
AU - Oberg, A.L.
AU - Orlow, I.
AU - Peters, U.
AU - Porta, M.
AU - Rabe, K.G.
AU - Rothman, N.
AU - Scelo, G.
AU - Sesso, H.D.
AU - Silverman, D.T.
AU - Thompson, I.M.
AU - Tjønneland, A.
AU - Trichopoulou, A.
AU - Wactawski-Wende, J.
AU - Wentzensen, N.
AU - Wilkens, L.R.
AU - Yu, H.
AU - Zeleniuch-Jacquotte, A.
AU - Amundadottir, L.T.
AU - Jacobs, E.J.
AU - Petersen, G.M.
AU - Wolpin, B.M.
AU - Risch, H.A.
AU - Chatterjee, N.
AU - Klein, A.P.
AU - Li, D.
AU - Kraft, P.
AU - Wei, P.
JO - Cancer Epidemiology Biomarkers and Prevention
PY - 2020
VL - 29
TODO - 9
SP - 1784-1791
PB - American Association for Cancer Research Inc.
SN - null
TODO - 10.1158/1055-9965.EPI-20-0275
TODO - Article;  cohort analysis;  controlled study;  diabetes mellitus;  female;  gene frequency;  gene linkage disequilibrium;  genome-wide association study;  genotype;  genotype environment interaction;  human;  major clinical study;  male;  obesity;  pancreas cancer;  priority journal;  single nucleotide polymorphism;  case control study;  diabetes mellitus;  genetics;  genome-wide association study;  obesity;  procedures;  risk factor, Case-Control Studies;  Diabetes Mellitus;  Female;  Genome-Wide Association Study;  Humans;  Male;  Obesity;  Risk Factors
TODO - 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: We conducted a gene–environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) 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: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 106) was observed in the meta-analysis (PGxE ¼ 1.2 106, PJoint ¼ 4.2 107). 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. © 2020 American Association for Cancer Research.
ER -