Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

In pancreatic ductal adenocarcinoma (PDA) evidence on the etiopathogenic role of past medical conditions in the occurrence and persistence of K-ras mutations is scant. Incident cases of PDA were interviewed face-to-face about past medical history and other factors. Logistic regression was used to compare PDA cases (n = 120) with wild-type and mutated K-ras tumors (case-case study). Patients with wild-type K-ras tumors were more likely to have a prior diagnosis of pancreatitis (Odds ratio [OR] = 6.11, p = 0.041). Diabetes mellitus (DM) was non-significantly more common among cases with a K-ras wild-type tumor, and the OR for DM of > 6 years of duration was 4.54 (p = 0.39). Patients with wild-type K-ras were significantly more likely to have had a surgically treated peptic ulcer (OR = 9.03, p = 0.027). The probability of having a K-ras wild-type tumor increased with the number of medical conditions (p for trend = 0.012); the corresponding OR for two or more medical conditions was 4.46 (95% CI: 1.37-14.50). Results raise the hypothesis that pancreatitis and possibly peptic ulcer might influence pancreatic carcinogenesis through pathways independent of K-ras mutation, perhaps related to growth factors or mediators of the inflammatory response. Large unselected studies should be conducted to refute or replicate our findings.