Similar to other digestive tract cancers, pancreatic cancer rates increase exponentially with age. Indeed, increasing age is the strongest known risk factor for pancreatic cancer; unfortunately, this risk factor is irreversible. The mean age at onset of pancreatic cancer is in the mid-60s, with only 10% of patients developing the tumor at or younger than age 50. In developed countries, cumulative risks (i.e., the probability of developing pancreatic cancer up to a given age, such as 65 or 70 years) is generally <1% for males and slightly less for females. Globally, the cumulative risk is 0.2% for males and 0.1% for females.

At present, surgery offers the best hope for increased survival from pancreatic cancer. However, the bulk of pancreatic cancer unfortunately occurs in elderly patients who often suffer from additional comorbidities, making them unsuitable for surgery. As an example, in New York State for the year 2001, only 15% of all patients with a diagnosis of pancreatic cancer underwent pancreatectomy—the best procedure for increasing survival.

There are observable gender-specific differences in the overall frequency of pancreatic cancer (Table 24.1). A small fraction of these differences may be related to hormonal variations between males and females, but because smoking is the best known risk factor for pancreatic cancer, the main cause for the difference has to do with an excess of smoking in males as compared with females.

Rates for pancreatic cancer are different in different racial groups. Black/white differences are particularly striking. For example, in a study from California, Chang et al. found that pancreatic cancer rates were about 50% higher in African Americans than in Caucasians (Table 24.2). Asian populations had the lowest rates (2). The explanation is not clear but could be due to racial differences in frequency of previously recognized risk factors (3).

Internationally, there are rather marked differences in mortality rates of pancreatic cancer (Table 24.3, Fig. 24.1). Low rates are found in Africa and parts of Asia; high rates are found in Australia/New Zealand, Europe, and North America. The average world age-standardized mortality rate is about 4.5/100,000/year.

Of the several risk factors that are known to be linked with pancreatic cancer, smoking has been the most extensively studied. Research on smoking and lung cancer published in the 1960s led to an early publication on smoking as a risk factor for pancreatic cancer. Based on a case-control study of 100 patients with biopsy-proven pancreatic tumors and 194 control subjects, Wynder et al. detected a twofold increase in the risk of pancreatic cancer (6). This finding has been confirmed in nearly all subsequent publications that examined the relationship between smoking and lung cancer. The main findings are as follows:

Heavy consumption of alcohol is the most common known risk factor for chronic pancreatitis, so it is reasonable to assume that alcohol might be a risk factor for pancreatic cancer. However, numerous studies of moderate drinkers have failed to find any link between consuming alcohol and pancreatic cancer. The best explanation is that the pancreas must be less sensitive to the toxic effects of alcohol than, say, the liver, where an occasional moderate drinker develops alcohol-induced cirrhosis eventually leading to liver cancer.

Because heavy drinkers are nearly always heavy smokers, it is likely that any putative association between heavy drinking and pancreatic cancer can be explained by tobacco exposure, rather than by alcohol.

For many reasons, finding reliable evidence linking diet with pancreatic cancer has been difficult. Because the disease is so aggressive, recruitment of patients for case-control studies has been difficult and is certain to introduce unavoidable biases favoring patients with less aggressive disease. In any event, case-control studies are likely to be less informative than prospective studies, but only a few prospective studies have been performed because they are costly, time consuming, and require extremely accurate follow-up over prolonged time periods. For cancer to develop after any putative risk factor, there must be a prolonged exposure period. This causes a final difficulty—it is difficult to measure early dietary exposure, which is likely to be at least if not more important than recent dietary intake.

In one large prospective study performed in male smokers, a high intake of saturated fat increased the risk of pancreatic cancer by 40%. However, a strange finding in this study was that high intake of energy and carbohydrates lowered the risk (9). In another large prospective study of more than 124,000 persons, Michaud et al. failed to find any relationship between dietary patterns and the risk of pancreatic cancer (10). In contrast, a case-control study performed by Nkondjock et al. found that consumption of fruits and vegetables reduced the risk of pancreatic cancer (11). Omega-3 fatty acids have been suspected to be a beneficial dietary component, but a recent meta-analysis failed to find any reduction in the risk of pancreatic cancer (12).

Do dietary supplements reduce the risk of pancreatic cancer? This important area has been inadequately studied; one report suggests that neither beta-carotene nor alpha-tocopherol have any impact on the risk of pancreatic cancer (13).