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


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Crous-Bou
Marta
M
Clinical & Molecular Epidemiology of Cancer Unit, Institut Municipal d'Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Carrer del Dr. Aiguader 88, 08003 Barcelona, Spain.
Porta
Miquel
M
Morales
Eva
E
López
Tomàs
T
Carrato
Alfredo
A
Puigdomènech
Elisa
E
Real
Francisco X
FX
D021441:Carcinoma, Pancreatic Ductal / Q000209:etiology* / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007407:Interviews as Topic; D008487:Medical History Taking; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics*; D010195:Pancreatitis / Q000150:complications; D010437:Peptic Ulcer / Q000150:complications