Table 1 Novel pancreatic cancer genetic susceptibility hits prioritized by approaches 1D, 2D, and 3D, as well as by in silico functional analyses
From: A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer
Genomic location | No. of prioritized novel SNPs | Nearest gene | Selection approach | Relevance in pancreas physiology or carcinogenesis |
|---|---|---|---|---|
1:150902203, 150974311 | 2 | SETDB1, FAM63A/MINDY1 | 1D, 2D | Histone methyltransferase that cooperates in the development of PC; lysine 48 deubiquitinase |
1:200016460 | 1 | NR5A2 | 1D, 2D | Transcription factor required for acinar differentiation and PC susceptibility gene |
2:120278171 | 1 | SCTR | 1D | Secretin receptor expressed in ductal cells |
6:108238917 | 1 | SEC63 | 1D | ER protein involved in ER stress response |
6:117150008 | 1 | GPRC6A | 2D | Disease-causal variant (CADD score = 35) |
6:117196211 | 1 | RFX6 | 2D | Transcription factor involved in pancreatic development and adult endocrine cell function |
8:128302062-128494384 | 27 | CASC8 | 1D, 2D | LncRNA cancer associated susceptibility gene |
9:21967751-21995300 | 6 | CDKN2A | 2D | Tumor suppressor mutated in > 95% of PC; also involved in familial PC |
9:6772101, 6785243, 6831637 | 3 | KDM4C | 2D | Highly expressed in PC |
9:94601093, 94603970 | 2 | ROR2 | 2D | Wnt pathway (activated in PC) |
11:60197299 | 1 | MS4A5 | 2D | Disease-causal variant (CADD score = 24.4) |
13:46446427, 46405544, 46471859-46511859 | 2/CIR | SIAH3 | 2D, 3D | E3 ubiquitin ligase |
16:67387817, 67397580 | 2 | LRRC36 | 2D | Disease-causal variant (CADD score = 24.4) |
16:75263661, 75295639, 75201482-75241482 | 2/CIR | BCAR1/CTRB2 | 2D, 3D | CTRB2 is chymotrypsinogen 2, a major pancreatic protease; associated with chronic pancreatitis and PC |
17:143542 | 1 | RPH3AL | 1D | Regulatory variant; rabphilin 3a is involved in exocytosis in acinar cells |
22:28476910-29165195 | CIR | MN1 | 3D | No pancreas-related function has been discovered so far |
22:28602352-28642352 | CIR | XBP1 | 3D | Major regulator of the ER stress and unfolded protein responses in acinar cells |