Interrelation of Energy Intake, Body Size, and Physical Activity with Prostate Cancer in a Large Prospective Cohort Study

Energy restriction reduces prostate tumor growth in transplantable tumor models in rodents, which suggests that excessive energy intake may contribute to the risk of prostate cancer. The association of total energy intake across the normal range with prostate cancer has not been consistent in epidemiological studies. We prospectively evaluated the joint associations of energy intake and body size or physical activity with prostate cancer. Participants were 46,786 male health professionals ages 40-75 years at baseline in 1986 who were free of cancer diagnosis. Between 1986 and 2000, we documented 2896 incident prostate cancer cases (excluding stage T1a) by review of medical records and histopathology reports. Of these, 339 were metastatic or fatal cases. We used Cox proportional hazards regression to estimate the multi-variate relative risk (RR) of prostate cancer associated with energy intake measured using a food frequency questionnaire, overall and stratified by body mass index, waist size, physical activity, as well as by age and family history of prostate cancer. There was no association between energy intake and total prostate cancer incidence. However, a modest increased risk of metastatic or fatal disease with energy intake was suggested [RR comparing extreme quintiles: 1.38, 95% confidence interval (CI) 0.96-1.98, P(trend) = 0.06]. This association was most pronounced in men with a lower body mass index (in stratum < 24 kg/m²: RR = 1.76, 95% CI 0.92-3.39; P(interaction) = 0.04) smaller waist size [in stratum ≤ 37 inches: RR = 1.91, 95% CI 0.83-4.36; P(interaction) = 0.03], and who were more physically active [in stratum ≥ median: RR = 1.74, 95% CI 0.93-3.26; P(interaction) = 0.09]. Also, the association of energy intake with metastatic and fatal prostate cancer was restricted to men who were younger [in stratum ≤ 65 years old: RR = 2.60, 95% CI 1.26-5.39; P(interaction) = 0.04] or who had a positive family history [RR = 3.33, 95% CI 1.26-8.76; P(interaction) = 0.04]. Although energy intake is known to be imperfectly measured by questionnaire, we observed a positive association between energy intake and metastatic or fatal prostate cancer among men who were leaner, more physically active, younger, and who had a family history of prostate cancer. Our observations suggest the testable hypothesis that the elevated risk of clinically important prostate cancer in men with a high energy intake may be attributable to certain metabolic profiles that favor enhanced growth factor production over an increase in adiposity.