Early onset pancreatic cancer: evidence of a major role for smoking and genetic factors.

Pancreatic cancer ranks 4th as a cause of cancer mortality and in approximately 5% to 10% of patients, this lethal tumor develops before age 50. We used age-, sex-, and country-specific cancer incidence and mortality data to describe the burden of early onset pancreatic cancer (EOPC) worldwide. We also reviewed the current published evidence on smoking and genetic factors associated with EOPC. We found an excess of EOPC resulting in a substantial number of years-of-life-lost in countries from Central and Eastern Europe. Worldwide, the proportion of EOPC is strongly correlated with lung cancer mortality (R(2) = 0.53), suggesting that approximately half of the variation in the proportion of EOPC could be explained by smoking. The unusual pattern of the incidence of pancreatic cancer by gender and race supports the primary role of smoking in the etiology of EOPC: the excess male-to-female rate ratio, attributable mainly to smoking, gradually approaches unity with increasing age. Moreover, male-to-female rate ratios are greater in blacks than in whites only in younger patients. Published studies also identified genetic alterations involved either alone or in association with smoking in the development of EOPC. In conclusion, EOPC constitutes only 1% to 5% of the total deaths from pancreatic cancer worldwide, but is responsible for 20% to 30% of the total number of years-of-life-lost caused by the disease. Smoking and genetic mutations are the major identified risk factors and seem to be even more important for EOPC than for PC in older age groups.