Molecular epidemiology of pancreatic cancer.
Pancreatic cancer is a leading cause of cancer-related death in this country. There are no early screening tests and no effective treatment options for this deadly disease. Prevention of pancreatic cancer is difficult because little is known about the etiology. Main risk factors for pancreatic cancer include cigarette smoking, dietary factors, and maybe occupational exposure to certain carcinogens. A few molecular epidemiologic studies of pancreatic cancer have been conducted so far. Although these studies have had a very limited sample size, they have provided some clues to the etiology. DNA adducts derived from exposure to polycyclic aromatic hydrocarbon and aromatic amines have been detected in pancreatic tissues in relation to the cancer risk. Oxidative DNA damage and lipid peroxidation-induced DNA adducts are also shown to be present in the pancreas. The level of aromatic DNA adducts has been correlated with the spectrum of K-ras mutation in the tumor. The mutation profiles of p53 and K-ras genes in pancreatic cancer resemble that in bladder cancer rather than that in lung cancer. The high proportion of G to A transition in pancreatic cancer suggests the involvement of nitrosamines or alkylating agents in pancreatic carcinogenesis. This notion was supported bythe observation that individuals with deficient repair of the DNA alkylation products seemed to have an increased risk for pancreatic cancer. K-ras mutation in pancreatic cancer has also been associated with alcohol consumption, organochlorines, and dietary habits. The associations between these environmental factors and K-ras mutations suggest that the mortality of pancreatic cancer can be decreased by changing of behavior and reducing exposure to environmental carcinogens.
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Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens; D018736:DNA Adducts / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D015227:Lipid Peroxidation; D017720:Molecular Epidemiology; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics
D014408:Biomarkers, Tumor; D002273:Carcinogens; D018736:DNA Adducts