The recent emergence of the importance of inherited genetic abnormalities in gastrointestinal tract neoplasia has led to closer investigation of the potential role for heritable factors in pancreatic cancer. Several rare hereditary disorders predispose persons to both endocrine and exocrine pancreatic cancer. These include the multiple endocrine neoplasia type I syndrome, hereditary pancreatitis, Lynch syndrome II, von Hippel-Lindau syndrome, ataxia-telangiectasia, and possibly the familial atypical multiple mole melanoma syndrome. In addition, case reports and formal epidemiologic studies have suggested the possibility of familial aggregations of pancreatic cancer outside the context of these rare familial syndromes. One case-control study estimated that 3% of pancreatic cancers had a hereditary origin. Evaluation of approximately 30 extended families with presumed familial pancreatic cancer has suggested that transmission is consistent with an autosomal dominant pattern. The age at onset, tumor histopathology, male preponderance, and overall survival of persons affected by pancreatic cancer in these families are reported to be similar to those of persons with pancreatic cancer in the general population. Continued study of these patients and their families may provide insight into the critical molecular genetic abnormalities leading to familial pancreatic cancer. Familial genetic abnormalities may then provide insight into the process of pancreatic carcinogenesis for patients with sporadic pancreatic cancer and provide opportunities for early detection and chemoprevention.
Exposure to certain chemicals, usually in a manufacturing setting, has been associated with an increased risk of pancreatic cancer. Previous studies implicated 2-naphthylamine, benzidine, and derivatives of gasoline. More recently, a cohort mortality study of more than 5000 chemical manufacturing workers suggested that heavy and prolonged exposure to DDT and related compounds can cause pancreatic cancer in humans. Finally, specific occupations (e.g., stone miners, cement workers, gardeners, and textile workers) have been associated with an increased risk of pancreatic cancer; however, the specific causative factors or carcinogens accounting for this increase are unclear. Currently, most newly diagnosed patients with pancreatic cancer do not have evidence of a specific chemical exposure or relevant occupational history. Other factors, such as smoking and diet, will probably play a much greater overall role in determining individual risk of pancreatic cancer.