A prospective study of calcium intake and incident and fatal prostate cancer.

Prostate cancer is the most common incident cancer and the second leading cause of cancer mortality in U.S. males. Higher milk intake has been relatively consistently associated with an increased risk of prostate cancer, especially advanced prostate cancer. Some data suggest that high intake of calcium might account for this association, but this relationship remains controversial. We hypothesized that high calcium intake, possibly by lowering 1,25(OH)2 vitamin D levels, is associated with poorer differentiation in prostate cancer and thereby with fatal prostate cancer. We examined calcium intake in relation to prostate cancer risk using data from the Health Professionals Follow-up Study, a prospective cohort study of 47,750 male health professionals with no history of cancer other than nonmelanoma skin cancer at baseline. We assessed total, dietary, and supplementary calcium intake in 1986, 1990, 1994, and 1998, using a validated food frequency questionnaire. We calculated the multivariable relative risk (RR) and 95% confidence intervals (95% CI) using Cox proportional hazards regression. Over 16 years of follow-up, we identified 3,544 total cases of prostate cancer, 523 advanced (extraprostatic) cases, and 312 fatal cases. Higher calcium intake was not appreciably associated with total or nonadvanced prostate cancer but was associated with a higher risk of advanced and fatal prostate cancer [for fatal prostate cancer, compared with men whose long-term calcium intake was 500-749 mg/d (excluding supplement use of <5 years); those with intakes of 1,500-1,999 mg/d had a RR, 1.87; 95% CI, 1.17-3.01; and those with > or = 2,000 mg/d had a RR, 2.43; 95% CI, 1.32-4.48; P(trend) = 0.003]. Dietary calcium and supplementary calcium were independently associated with an increased risk. For high-grade prostate cancer (Gleason > or = 7), an association was observed for high versus low calcium intake (RR, 1.89; 95% CI, 1.32-2.71; P(trend) = 0.005), but a nonsignificant, inverse association was observed for organ-confined, low-grade prostate cancer (RR, 0.79; 95% CI, 0.50-1.25; P(trend) = 0.09). In a sample of this cohort, higher calcium intake was associated with lower circulating 1,25(OH)2 vitamin D levels. Our findings suggest that calcium intakes exceeding 1,500 mg/d may be associated with a decrease in differentiation in prostate cancer and ultimately with a higher risk of advanced and fatal prostate cancer but not with well-differentiated, organ-confined cancers.