Familial pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer death in both men a nd women in the United States and will be responsible for an estimated 28,9 00 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a f amily history of the disease. A small fraction of this aggregation can be a ccounted for in inherited cancer syndromes, including familial atypical mul tiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian canc er, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, p16 (familial atypical multiple-mole melanoma), mismatch repair (hereditary non polyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with app arently sporadic pancreatic cancer. Many patients with pancreatic cancers c aused by a germline mutation in a cancer-causing gene do not have a pedigre e that is suggestive of a familial cancer syndrome. A recent prospective an alysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multip le first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians targ et screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.