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Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer

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Abstract

Purpose

To assess whether calcium intake and common genetic variants of the calcium-sensing receptor (CASR) are associated with either aggressive prostate cancer (PCa) or disease recurrence after prostatectomy.

Methods

Calcium intake at diagnosis was assessed, and 65 common single-nucleotide polymorphisms (SNPs) in CASR were genotyped in 886 prostatectomy patients. We investigated the association between calcium intake and CASR variants with both PCa recurrence and aggressiveness (defined as Gleason score ≥4 + 3, stage ≥pT3, or nodal-positive disease).

Results

A total of 285 men had aggressive disease and 91 experienced recurrence. A U-shaped relationship between calcium intake and both disease recurrence and aggressiveness was observed. Compared to the middle quintile, the HR for disease recurrence was 3.07 (95 % CI 1.41–6.69) for the lowest quintile and 3.21 (95 % CI 1.47–7.00) and 2.97 (95 % CI 1.37–6.45) for the two upper quintiles, respectively. Compared to the middle quintile, the OR for aggressive disease was 1.80 (95 % CI 1.11–2.91) for the lowest quintile and 1.75 (95 % CI 1.08–2.85) for the highest quintile of calcium intake. The main effects of CASR variants were not associated with PCa recurrence or aggressiveness. In the subgroup of patients with moderate calcium intake, 31 SNPs in four distinct blocks of high linkage disequilibrium were associated with PCa recurrence.

Conclusions

We observed a protective effect of moderate calcium intake for PCa aggressiveness and recurrence. While CASR variants were not associated with these outcomes in the entire cohort, they may be associated with disease recurrence in men with moderate calcium intakes.

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Acknowledgments

The authors declare that they have no conflict of interest. Moritz Binder was supported by a German Academic Exchange Service Scholarship. Irene M. Shui was supported by a United States Army Department of Defense Prostate Cancer Postdoctoral Fellowship. Kathryn M. Wilson, Kathryn L. Penney, and Lorelei A. Mucci were supported by Prostate Cancer Foundation Young Investigator Awards. Biomarker work in the Division of Urology is supported by Anthony DiNovi and David McGraw.

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Authors and Affiliations

  1. Master of Public Health Program, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Moritz Binder

  2. Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Irene M. Shui, Kathryn M. Wilson, Kathryn L. Penney & Lorelei A. Mucci

  3. Channing Division of Network Medicine, Brigham & Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02215, USA

    Kathryn M. Wilson, Kathryn L. Penney & Lorelei A. Mucci

  4. Division of Urologic Surgery, Brigham and Women’s Hospital, 45 Francis Street, Boston, MA, 02115, USA

    Adam S. Kibel

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  1. Moritz Binder
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Correspondence to Adam S. Kibel.

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Binder, M., Shui, I.M., Wilson, K.M. et al. Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer. Cancer Causes Control 26, 1751–1759 (2015). https://doi.org/10.1007/s10552-015-0668-3

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