Molecular epidemiology of pancreatic cancer.
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Currently there is no early diagnostic test and no effective treatment options for this deadly disease. Prevention of pancreatic cancer is difficult because little is known about its etiology. The main modifiable risk factors for pancreatic cancer include cigarette smoking and dietary factors. Information from molecular epidemiological study of pancreatic cancer is very limited. DNA adducts derived from exposure to polycyclic aromatic hydrocarbon, aromatic amines, and heterocyclic amines have been detected in human pancreatic tissues. DNA damages derived from oxidative stress and lipid peroxidation are also present in the pancreas. No study has demonstrated a main effect of carcinogen-metabolizing genes and DNA repair genes on the risk of pancreatic cancer thus far. However, significant effects of these genes have been observed among individuals with known carcinogen exposure, such as smoking. A number of environmental and lifestyle factors, such as smoking, alcohol, coffee consumption, and exposure to organochlorine or hydrocarbon solvent, have been associated with the frequency and spectrum of K-ras mutation in pancreatic tumors. Dietary folate intake and serum levels of folate have been associated with the risk of pancreatic cancer among male smokers. These findings demonstrate the potential of the molecular epidemiology approach in understanding the etiology of pancreatic cancer. Further efforts should be made to understand the interactive relationship between genetic and environmental factors in the etiology of pancreatic cancer, which will in turn be important in identifying the high-risk population for the primary prevention of this deadly disease.
Li
Donghui
D
Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 426, Houston, TX 77030, USA. dli@mdanderson.org
Jiao
Li
L
D002273:Carcinogens; D018736:DNA Adducts; D004249:DNA Damage; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
D002273:Carcinogens; D018736:DNA Adducts