Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer.
Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer.
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DOI：
10.1007/s10552-015-0668-3
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Kibel AS
中科院分区：
文献类型：
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作者：
Binder M;Shui IM;Wilson KM;Penney KL;PRACTICAL/ELLIPSE Consortium;Mucci LA;Kibel AS
评估钙摄入量和钙敏感受体(CaSR)的常见遗传变异是否与侵袭性前列腺癌(PCa)或前列腺癌切除术后疾病复发有关。对886例前列腺癌患者诊断时的钙摄入量进行了评估，并对CASR中65个常见的单核苷酸多态性(SNPs)进行了基因分型。我们调查了钙摄入量和CaSR变异与前列腺癌复发和侵袭性(定义为格里森评分≥4+3，≥PT3期，或结节阳性疾病)之间的关系。共有285名男性患有侵袭性疾病，91人复发。观察到钙摄入量与疾病复发和侵袭性之间呈U型关系。与中五分位数相比，最低五分位数的疾病复发比为3.07(95%CI 1.41~6.69)，较高的五分位数为3.21(95%CI 1.47~7.00)和2.97(95%CI 1.37~6.45)。与中间五分位数相比，钙摄入量最低的五分位数的侵袭性疾病的OR为1.80(95%CI 1.11~2.91)，而钙摄入量最高的五分位数的OR为1.75(95%CI 1.08~2.85)。CASR变异的主要作用与PCa复发或侵袭性无关。在中等钙摄入量的患者亚组中，4个不同的高连锁不平衡区块中的31个SNPs与PCa复发相关。我们观察到适量的钙摄入对前列腺癌的侵袭性和复发率有保护作用。虽然在整个队列中，CaSR变异与这些结果无关，但在中等钙摄入量的男性中，它们可能与疾病复发有关。
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. 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). 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. 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.