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Cancer Causes Control. 2015 Dec;26(12):1751-9. doi: 10.1007/s10552-015-0668-3. Epub 2015 Sep 25.

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

Author information

1
Master of Public Health Program, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
2
Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
3
Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02215, USA.
4
Division of Urologic Surgery, Brigham and Women's Hospital, 45 Francis Street, Boston, MA, 02115, USA. akibel@partners.org.

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.

KEYWORDS:

Calcium intake; Calcium-sensing receptor; Clinical outcomes; Prostate cancer; Single-nucleotide polymorphism

PMID:
26407952
PMCID:
PMC4633306
DOI:
10.1007/s10552-015-0668-3
[Indexed for MEDLINE]
Free PMC Article

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