The association between selected risk factors for pancreatic cancer and the expression of p53 and K-ras codon 12 mutations.
BACKGROUND
Pancreatic cancer is a major contributor to cancer mortality. Studies suggest that a few risk factors, including cigarette smoking, body mass index, having a relative with pancreatic cancer, and diabetes may be related to pancreatic cancer risk.


OBJECTIVE
We conducted a case-control study in southeastern Michigan to examine the relation between the above mentioned risk factors and mutations of the K-ras oncogene and p53 tumor suppressor gene.


METHODS
Two hundred forty-five patients with newly diagnosed pancreatic cancer and 420 general population controls were enrolled in the study. For this analysis, all case subjects were restricted to the pancreatic cancer patients that had tissue blocks available for study (n = 51). In-person interviews were conducted to ascertain information on demographic and lifestyle factors. Adjusted logistic regression analyses were conducted to compare various subject characteristics of pancreatic cancer patients with K-ras and p53 mutations and their subtypes to the characteristics of the general population controls.


RESULTS
Smoking (adjusted odds ratio [aOR] = 2.0; 95% confidence interval [95%CI] = 0.9-4.3) and diabetes diagnosed 5 or more years before interview (aOR = 3.4; 95%CI = 1.3-8.8) were associated with pancreatic cancer patients positive for K-ras codon 12 mutations, but not with pancreatic cancer patients negative for K-ras codon 12 mutations. On the other hand, none of the examined risk factors were meaningfully related to patients with p53 mutations.


CONCLUSIONS
This study suggests that some recognized risk factors for pancreatic cancer may also be associated with K-ras codon 12 mutations. However, further large-scale studies are warranted.
Department of Environmental Health Sciences, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, MI 48109-2029, USA.
Jon P
JP
Fryzek
David H
DH
Garabrant
Maryjean
M
Schenk
Margaret
M
Kinnard
Joel K
JK
Greenson
Fazlul H
FH
Sarkar
D000230:Adenocarcinoma / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53