Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4)

Abstract

Background: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction.

Patients and methods: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Results: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006).

Conclusions: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Figure 1.

Forest plot of individual PanC4 studies—odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatitis (diagnosed >2 years before) and risk of pancreatic cancer. Study-specific ORs adjusted for age, sex, race/ethnicity, education, body mass index, tobacco smoking, alcohol intake and history of diabetes. Squares indicate study-specific OR; size of the square denotes weight given to this study (inverse of the variance of the log OR). Horizontal lines indicate study-specific CI; diamond indicates summary pooled OR, adjusted for age, sex, study, race/ethnicity, education, body mass index, tobacco smoking, alcohol intake and history of diabetes. Solid vertical line denotes OR of 1. Dashed vertical line denotes summary OR.