Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer.
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.
['Binder|Moritz|M|', 'Shui|Irene M|IM|', 'Wilson|Kathryn M|KM|', 'Penney|Kathryn L|KL|', '|||', 'Mucci|Lorelei A|LA|', 'Kibel|Adam S|AS|']
D000328:Adult D000368:Aged D002118:Calcium D014644:Genetic Variation D005838:Genotype D006801:Humans D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009364:Neoplasm Recurrence, Local D020641:Polymorphism, Single Nucleotide D011468:Prostatectomy D011471:Prostatic Neoplasms D044169:Receptors, Calcium-Sensing
Calcium intake Calcium-sensing receptor Prostate cancer Single-nucleotide polymorphism Clinical outcomes