Table 4:

Risk factors for pancreatic cancer

Risk Factor	Prevalence and Associated Risk	References
Non-genetic
Cigarette Smoking	1.7 fold increased risk vs to never smokers.	[161]
Family history of pancreatic cancer	2.5 fold increased risk for individuals with a first degree relative with pancreatic cancer, risk increases with additional affected relatives and/or family members who developed cancer before age 50.	[162]
Long Standing Diabetes	1.5 – 2-fold increased risk of PDAC for individuals with diabetes >3 years in duration.	[163–166]
New onset Diabetes	<0.3% to 0.8% of new diabetes develop pancreatic ductal adenocarcinoma primarily within one year of diabetes diagnosis.	[143,167,168]
Obesity	1.6 fold increased risk in obese vs normal weight.	[169]
Genes
ATM pathogenic variant	Occurs in 1–3% of PDAC cases, 6.5 fold increased risk.	[170–172]
BRCA1	Occurs in 1% of PDAC, 2–4 fold increased risk.	[173–176]
BRCA2 pathogenic variant	Occurs in 2–7% of PDAC cases, 3.5–10 fold increased risk.	[174–180]
CDKN2A pathogenic variant	Occurs <0.5% of PDAC cases, 34 -fold increased risk.	[175,181]
CPA1/CPB1 variants	<1%; lifetime risk not defined	[182,183]
GWAS Variants & Polygenic Risk Scores	European ancestry populations: 1q32.1 (NR5A2), 1p36.33 (NOC2L), 2p13.3 (ETAA1), 3q29 (TP63), 5p15.33 (CLPTM1L, TERT), 7p14.1 (INHBA), 8q21.11 (HNF4G) 8q24.21 (MYC), 9q34.2 (ABO), 13q12.2 (PDX1), 13q22.1 (KLF5), 16q23.1 (BCAR1), 17q12 (HNF1B) 17q25.1 (LINC00673), 18q21.32 (GRP), and 22q12.1 (ZNRF). China: 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11: Japan 6p25.3, 12p11.21 and 7q36.2. In Europeans ~4 fold higher risk for those with the top 10% of polygenic risk (combined weighted average of associated loci).	[184–189]
Mismatch Repair Gene	Occurs in up to 1% of PDAC, 8 fold increased risk.	[190]
PALB2 pathogenic variant	Occurs <0.5% of PDAC cases, up to 10-fold risk.	[191]
PRSS1	Very Rare; >40 fold.	[192–194]
STK11	Very Rare: 10–40 fold.	[195–197]