Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2

Abstract

Background: Prostate cancer is the most common noncutaneous cancer in American males. Causal links between dairy, or dietary calcium, and this cancer are considered suggestive but limited.

Objectives: To evaluate these associations in a large North American cohort, including many with no (or very low) dairy intake and much calcium from nondairy sources.

Methods: A prospective cohort study of 28,737 Seventh-day Adventist men in the United States and Canada, of whom 6389 were of black ethnicity. Diet was measured by FFQ, and 275 male participants also provided repeated 24-h dietary recalls as a calibration substudy. Incident cancers were mainly found by matching with cancer registries. Analyses used multivariable proportional hazards regressions and regression calibration for some analyses.

Results: In total, 1254 (190 advanced) incident prostate cancer cases were found during an average 7.8 y of follow-up. Men at the 90th percentile of dairy intake (430 g/d) compared with the 10th percentile (20.2 g/d) had higher prostate cancer risk (HR: 1.27; 95% CI: 1.12, 1.43). Similar findings, comparing the same g/d intakes, were demonstrated for advanced prostate cancers (HR: 1.38; 95% CI: 1.02, 1.88), for nonadvanced cases (HR: 1.27; 95% CI: 1.11, 1.45), in black participants (HR: 1.24; 95% CI: 0.98, 1.58), and when excluding vegan participants (HR: 1.22; 95% CI: 1.03, 1.43). Calibrated dairy (g/d) regressions (all participants and all prostate cancers), adjusting for dietary measurement error, found a HR of 1.75 (95% CI: 1.32, 2.32). Comparing 90th percentile intake to zero intakes (uncalibrated), the HR was 1.62 (95% CI: 1.26, 2.05). There was no evidence of an effect of higher (905 mg/d) compared with lower (349 mg/d) intakes of nondairy calcium (HR: 1.16; 95% CI: 0.94, 1.44).

Conclusions: Men with higher intake of dairy foods, but not nondairy calcium, had a higher risk of prostate cancer compared with men having lower intakes. Associations were nonlinear, suggesting greatest increases in risk at relatively low doses.

Keywords: African American; Seventh-day Adventists; calcium intake; cohort study; dairy intake; prostate cancer; regression calibration; vegans; vegetarians.

FIGURE 1

Restricted cubic splined and unsplined multivariable-adjusted associations between dairy consumption (g/d) and risk of prostate cancer (95% confidence bands for unsplined analysis). (A) With vegans included (N = 28,737). (B) With vegans excluded (N = 26,436). Reference value in parts A and B is the 10th percentile of intake of the population without vegans. Cox proportional hazards regressions. The calculation of hazards compares 430 g/d with 20.2 g/d total dairy intakes (90th compared to 10th percentiles of dairy users). Adjusted for age (attained age as time variable), race (black/nonblack), education (up to high school graduate, trade school/some college/associate degree, bachelor degree or higher), moderate or vigorous exercise (none, ≤60 min/wk, >60 min/wk), family history of prostate cancer (yes, no), history of benign prostatic hyperplasia (yes, no), prostate cancer screening, treated for diabetes mellitus within the past year (yes, no), height, BMI (in kg/m²; <25, 25–29.9, 30–34.9, ≥35), nondairy and supplemental calcium, and dietary energy (kcal). Also included are red meat, soy, cooked tomatoes, nuts and seeds, and legumes (no soy), measured in grams, as energy-adjusted and log-transformed continuous variables. Spline and unsplined models differ (likelihood ratio test of quadratic and cubic spline terms) using likelihood ratio tests: P = 0.78 (with vegans); P = 0.83 (without vegans). Interrupted lines indicate the 10th, 30th, 50th, 70th, and 90th percentiles of dairy intake in each plot. The asterisks show the positions of spline knots, with these positioned at percentiles 5.0, 27.5, 50.0, 72.5, and 95.0 of intake calculated for population of each plot.

FIGURE 2

Associations of total dairy (calibrated and uncalibrated) and subcategories of dairy foods (uncalibrated) with risk of prostate cancer (N = 28,737 participants and 1254 prostate cancer cases in all analyses). Adjusted for age (attained age as time variable), race (black/nonblack), education (up to high school graduate, trade school/some college/associate degree, bachelor degree or higher), moderate or vigorous exercise (none, ≤60 min/wk, >60 min/wk), family history of prostate cancer (yes, no), history of benign prostatic hyperplasia (yes, no), prostate cancer screening, treated for diabetes mellitus within the past year (yes, no), BMI (in kg/m²; <25, 25–30, >30), nondairy and supplemental calcium, and dietary energy (kcal). Also included are red meat, soy, cooked tomatoes, nuts and seeds, and legumes (no soy), measured in grams, as energy-adjusted and log-transformed continuous variables. When exposure variables were milk, cheese, yogurt, they are all included in the models, and hence are adjusted for each other. Statistical testing used Wald tests. Results are presented as Cox proportional hazards regressions and 95% CIs. “Upper” and “lower” columns refer to the upper and lower boundaries of the 95% CI for the HR. Hazard ratios compare risk in higher compared with lower intakes. Comparison points for the hazards are always the 90th and 10th percentiles of values for that dairy product among dairy users, except that for comparability, comparison points for total, full-fat, and reduced-fat dairy and milk always use comparison values for total dairy or milk, respectively. Comparison values on the FFQ scale are as follows: total dairy, full-fat dairy, and reduced-fat dairy, comparison 430 and 20.2 g/d; total dairy, full-fat dairy, and reduced-fat dairy energy, comparison 351 and 35.7 kcal/d. For total milk, full-fat milk, and reduced-fat milk, the comparisons are 345 and 6.19 g/d; the total milk energy comparison is 163 and 8.58 kcal/d. Comparisons are 46.1 and 2.03 g/d for cheese and 111 and 1.91 g/d for yogurt. The comparisons are 291 and 11.0 g/d for calibrated total dairy on the dietary recall scale and 305 and 27.0 kcal/d calibrated dairy energy on the dietary recall scale.