Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer
Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer
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DOI：
10.1158/0008-5472.can-04-3134
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Ingles, SA
中科院分区：
文献类型：
--
作者：
John, EM;Schwartz, GG;Ingles, SA
大量实验证据表明，激素形式的维生素D促进人类前列腺癌细胞的分化，抑制其增殖、侵袭和转移。维生素D状态和/或维生素D受体（VDR）多态性与前列腺癌风险的流行病学研究结果不一。我们对旧金山湾区40 - 79岁的晚期前列腺癌患者进行了一项基于人群的病例对照研究。905名非西班牙裔白人男性（450例和455例对照）收集了关于终生日晒和其他风险因素的访谈数据。使用反射计，我们测量了上臂下（防晒部位）的组成性皮肤色素沉着和前额（阳光暴露部位）的兼性色素沉着，并根据这些测量结果计算了阳光暴露指数。采集生物标本426例，对照组440例。对5‘调控区（Cdx-2）、外显子2 （FokI）和3’区（TaqI和BglI）的VDR多态性进行基因分型。晚期前列腺癌的风险降低与高日晒有关[比值比（OR）， 0.51；95%可信区间（95% CI）， 0.33-0.80)和高职业户外活动（OR, 0.73; 95% CI, 0.48-1.11）。在高日照条件下，高活性等位基因FokI FF或FF、TaqI tt和BglI BB基因型的风险显著降低，Cdx-2 AG或AA基因型的风险不显著降低，or范围为0.46至0.67。我们的研究结果支持了阳光照射和VDR多态性在前列腺癌病因学中共同发挥重要作用的假设。
Substantial experimental evidence indicates that the hormonal form of vitamin D promotes the differentiation I inhibits the proliferation, invasiveness, and metastasis of human prostatic cancer cells. Results from epidemiologic studies of vitamin D status and/or vitamin D receptor (VDR) polymorphisms and prostate cancer risk have been mixed. We conducted a population-based, case-control study of advanced prostate cancer among men ages 40 to 79 years from the San Francisco Bay area. Interview data on lifetime sun exposure and other risk factors were collected for 905 non-Hispanic White men (450 cases and 455 controls). Using a reflectometer, we measured constitutive skin pigmentation on the upper underarm (a sun-protected site) and facultative pigmentation on the forehead (a sun-exposed site) and calculated a sun exposure index from these measurements. Biospecimens were collected for 426 cases and 440 controls. Genotyping was done for VDR polymorphisms in the 5' regulatory region (Cdx-2), exon 2 (FokI), and the 3' region (TaqI and BglI). Reduced risk of advanced prostate cancer was associated with high sun exposure determined by reflectometry [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.33-0.80] and high occupational outdoor activity (OR, 0.73; 95% CI, 0.48-1.11). Significant risk reductions with the high-activity alleles FokI FF or Ff, TaqI tt, and BglI BB genotypes and a nonsignificant reduction with Cdx-2 AG or AA genotype were observed in the presence of high sun exposure, with ORs ranging from 0.46 to 0.67. Our findings support the hypothesis that sun exposure and VDR polymorphisms together play important roles in the etiology of prostate cancer.