Table 113 Risk factors for developing pancreatic cancer Environmental Factors

Definite Cigarette smoking Possible Excess dietary fats

Exposure to DDT and nonchlorinated solvents Host Factors

Chronic pancreatitis Genetic predisposition BRCA 2 mutations Hereditary pancreatitis Gardner's syndrome

Familial and atypical multiple mole melanoma (FAMMM) syndrome

Chronic pancreatitis has been associated with an increased risk for pancreatic cancer. However, most patients with pancreatitis never develop pancreatic cancer. Some studies suggest that the association of pancreatic cancer with pancreatitis is likely due to other associated risk factors such as cigarette smoking. In rare cases, some patients with familial forms of chronic pancreatitis are at high risk for developing cancer.

Patients who have had gastric resection to treat ulcers may have an increased risk for developing pancreatic cancer. Less consistently, some studies have identified that women who have undergone cholecystectomy are possibly at higher risk for later developing pancreatic cancer.

There appears to be some occupational risk for developing pancreatic cancer for those working in aluminum mining, the metal industries, the tanning industry and machine repair. Exposure to pesticides such as DDT, certain dyes and certain chemicals such as beta-naphthylamine and benzidine are thought to increase the risk of developing pancreatic cancer.

Between 5 and 10% of pancreatic cancer cases may be related to an inherited risk.

Recent research has demonstrated that many of the risk factors affect the DNA of pancreatic cells resulting in carcinogenesis. Mutations involving the K-ras gene are the most common abnormalities identified with a prevalence of 70-100%, higher than any other cancer type.

K-ras mutations are seen in ductal cells before the presence of invasive cancer and are often seen in chronic pancreatitis. This may be an early event in the patho-genesis of the disease that, when followed by other gene abnormalities, may lead to the development of an invasive tumor. Subsequent mutations in tumor suppressor genes may lead to deregulation of cell growth. A number of mutated tumor-suppressor genes have been identified, the most common being P16, P53 and DPC4 (deleted in pancreatic carcinoma locus 4). Men and women with BRCA2 mutations have a 10 to 20 times higher risk for developing pancreatic cancer than the general population. Patients with close relatives who have had breast or ovarian cancers may have BRCA2 mutations. Other inherited gene abnormalities associated with an increased risk of pancreatic cancer include hereditary pancreatitis, MEN1 (multiple

endocrine neoplasia type 1), Gardner's syndrome, nonpolyposis colorectal cancer (Lynch II variant) and familial and atypical multiple mole melanoma (FAMMM) syndrome.

Other than smoking cessation and a diet that is high in fresh fruits, vegetables, fiber and low in fat, there are no specific guidelines for preventing cancer of the pancreas.

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