Ma J, Stampfer M J, Gann P H, Hough H L, Giovannucci E, Kelsey K T, Hennekens C H, Hunter D J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Epidemiol Biomarkers Prev. 1998 May;7(5):385-90.
Prostatic cells express vitamin D receptor (VDR), which mediates the functions of 1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse associations between two VDR polymorphisms, TaqI and poly(A), and risk of prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In a case-control study nested in the Physicians' Health Study, a randomized double-blind trial of aspirin and beta-carotene among 22,071 United States male physicians, we examined the associations between BsmI and TaqI and prostate cancer risk and whether the associations varied according to age and vitamin D metabolite levels among 372 incident cases and 591 controls. Among controls, the BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02), suggesting an association of the VDR polymorphisms with VDR function. Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism). Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed no significant associations. However, in an analysis restricted to men with plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR = 0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype; the risk reduction was particularly marked among older men (RR = 0.18, 95% CI = 0.05-0.68). We did not observe this inverse association among men with 25-hydroxyvitamin D levels above the median, nor did we observe it among younger men.
前列腺细胞表达维生素D受体（VDR），该受体介导1,25 - 二羟基维生素D的功能。最近的两项病例对照研究表明，VDR的两种多态性，即TaqI和多聚腺苷酸（poly(A)），与前列腺癌风险之间存在强烈的负相关。这两种多态性以及第三种多态性BsmI紧密连锁。在医师健康研究中的一项病例对照研究中，该研究是对22,071名美国男性医师进行的阿司匹林和β - 胡萝卜素的随机双盲试验，我们在372例新发病例和591例对照中，研究了BsmI和TaqI与前列腺癌风险之间的关联，以及这些关联是否因年龄和维生素D代谢物水平而异。在对照组中，BB基因型与较高的1,25 - 二羟基维生素D显著相关（BB基因型的中位数为36.2 pg/ml，bb基因型为33.9 pg/ml；P = 0.02），这表明VDR多态性与VDR功能相关。总体而言，我们未观察到这些VDR多态性与前列腺癌风险之间存在显著关联：与bb基因型相比，BB基因型的相对风险（RR）= 0.86 [95%置信区间（CI）= 0.57 - 1.29]，Bb基因型的RR = 0.92（95% CI = 0.69 - 1.22）（TaqI多态性的结果类似）。按年龄（≤61岁和>61岁）和肿瘤侵袭性分层后未显示出显著关联。然而，在一项仅限于血浆25 - 羟基维生素D低于中位数的男性的分析中，我们观察到BB基因型男性与bb基因型男性相比，风险降低了57%（RR = 0.43，95% CI = 0.19 - 0.98）；这种风险降低在老年男性中尤为明显（RR = 0.18，95% CI = 0.05 - 0.68）。在25 - 羟基维生素D水平高于中位数的男性中，我们未观察到这种负相关，在年轻男性中也未观察到。
