This large study of men and women does not support the hypothesis that higher levels of physical activity and leaner body weight decrease the risk of pancreatic cancer. Individuals who satisfied recommendations for physical activity (Pate et al, 1995
) and/or a healthy BMI (WHO, 1995
) did not experience lower risk of pancreatic cancer than their less active and overweight peers.
Biologically, it appears plausible for physical activity and lean body weight to decrease pancreatic cancer risk. Physical inactivity and overweight are associated with abnormal glucose metabolism, with 90% of type II diabetics in the US being obese (Albu and Pi-Sunyer, 1998
). On the other hand, physical activity improves insulin action in overweight and obese individuals, even if body weight and composition are unchanged (Kelley and Goodpaster, 1999
). An abnormal insulin and glucose profile is related to increased risk of pancreatic cancer. Hamsters fed a high-fat diet experience peripheral insulin resistance and develop pancreatic cancers when exposed to a pancreatic carcinogen (Schneider et al, 2001
). However, if treated with metformin, which improves insulin sensitivity and can lead to lower insulin levels, the incidence of pancreatic cancer is very much reduced. Human pancreatic cancer cells possess insulin receptors, and dose-dependent increases in cell proliferation are observed in response to insulin (Fisher et al, 1996
). In humans, higher plasma glucose levels after an oral glucose load is predictive of pancreatic cancer mortality (Gapstur et al, 2000
), and a diagnosis of diabetes mellitus is associated with increased risk (Everhart and Wright, 1995
While the above data suggest that physical activity and body weight may have a role in the aetiology of pancreatic cancer, the findings from epidemiologic studies have been sparse and inconsistent. Three small studies reported no significant association between physical activity and risk (Paffenbarger et al, 1987
; Garfinkel and Stellman, 1988
; Waterbor et al, 1988
), as did a large study with 409 pancreatic cancer deaths (Brownson et al, 1991
). In contrast, a prospective study with 350 incident cases observed about a 30–40% reduction in risk among the most active subjects, especially those overweight (Michaud et al, 2001
). It is unclear why the present findings differ. Our a priori
calculations had estimated reasonable power to detect a 40% reduction in pancreatic cancer risk.
Previous studies of body weight and pancreatic cancer also have yielded inconsistent findings, with case–control studies being more likely to report no association (Howe et al, 1992
; Lyon et al, 1993
; Coughlin et al, 2000
; Michaud et al, 2001
). A possible explanation for the discrepancy may be that because of the high mortality from pancreatic cancer, case–control studies are limited by the information obtained from next of kin. However, this study that obtained information on weight prospectively and directly from subjects also did not observe any association with BMI.
Strengths of the present study include its large size and detailed physical activity information. As discussed, the prospective nature of this study limits potential bias from a high fatality rate among pancreatic cancer patients. Limitations include the self-reported information on physical activity and body weight. However, our physical activity assessment is reliable and valid for large population studies (Albanes et al, 1990
; Washburn et al, 1991
; Ainsworth et al, 1993b
). Self-reported body weight also correlates well with measured weights in a well-educated population (Rimm et al, 1990
). We were limited in our ability to examine the sexes separately because of the small number of cases in women (n
=5). Finally, we ascertained mortality not incidence, but this should not represent a major limitation since, with its high fatality rate, pancreatic cancer mortality would closely reflect incidence.
In conclusion, the data from this large study do not support the biologically plausible hypothesis that physical activity and lean body weight to reduce the risk of pancreatic cancer.