Table 1.

Novel pancreatic cancer genetic susceptibility hits prioritized by approaches 1D, 2D, and 3D, as well as by in silico functional analyses

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

PC pancreatic cancer, CIR chromatin interacting region