Xu Yue, Shibata Atsuko, McNeal John E, Stamey Thomas A, Feldman David, Peehl Donna M
Department of Urology, Stanford University School of Medicine, Stanford, California 94305, USA.
Cancer Epidemiol Biomarkers Prev. 2003 Jan;12(1):23-7.
Vitamin D plays an important role in cell growth and differentiation and is proposed to protect against cancer initiation and/or progression. The vitamin D receptor (VDR) has a thymine/cytosine (T/C) polymorphism located in the first of two potential start (ATG) codons that can be detected by a RFLP using the endonuclease FokI. The C variant, which lacks the first ATG, results in a shorter VDR and is referred to as the F allele. The T variant (f allele) initiates at the first ATG. We examined the association of the VDR FokI genotype with histopathological characteristics and prognosis of prostate cancer among 191 mostly Caucasian subjects who had undergone radical prostatectomy between 1984 and 1992. The frequencies of the FF, Ff, and ff genotypes were 41%, 38%, and 21%, respectively. Subjects with the ff genotype had a lower mean percentage of Gleason grade 4/5 cancer (30.3%) than subjects with the FF or Ff genotypes (42.8% and 43.8%, respectively; P = 0.015 by t test for ff versus FF + Ff). The data suggest that the presence of an F allele increased the risk of being diagnosed with more aggressive cancer because higher percentage of Gleason grade 4/5 is associated with worse prognosis. The age-adjusted risk of prostate-specific antigen failure was lower for the ff genotype than for the FF genotype by Cox proportional hazards analysis but did not achieve statistical significance (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32). This risk reduction disappeared after further adjustment for percentage of Gleason grade 4/5, cancer volume, and preoperative serum prostate-specific antigen level (hazard ratio = 1.03; 95% confidence interval, 0.58-1.85). In conclusion, the ff genotype was associated with less aggressive histopathological findings than Ff or FF genotypes. Additional studies with a larger sample size and investigation of the functional significance of the FokI polymorphism in prostate cancer cells are warranted.
维生素D在细胞生长和分化中起重要作用，并且被认为可以预防癌症的发生和/或进展。维生素D受体（VDR）在两个潜在起始（ATG）密码子中的第一个密码子处存在胸腺嘧啶/胞嘧啶（T/C）多态性，可使用核酸内切酶FokI通过限制性片段长度多态性（RFLP）检测到。缺乏第一个ATG的C变体导致VDR较短，被称为F等位基因。T变体（f等位基因）从第一个ATG开始。我们在191名主要为白种人且在1984年至1992年间接受了根治性前列腺切除术的受试者中，研究了VDR FokI基因型与前列腺癌组织病理学特征及预后的相关性。FF、Ff和ff基因型的频率分别为41%、38%和21%。ff基因型的受试者中Gleason 4/5级癌症的平均百分比（30.3%）低于FF或Ff基因型的受试者（分别为42.8%和43.8%；ff与FF + Ff相比，t检验P = 0.015）。数据表明，F等位基因的存在增加了被诊断为侵袭性更强癌症的风险，因为较高百分比的Gleason 4/5级与更差的预后相关。通过Cox比例风险分析，ff基因型的前列腺特异性抗原失败的年龄调整风险低于FF基因型，但未达到统计学显著性（风险比 = 0.76；95%置信区间，0.44 - 1.32）。在进一步调整Gleason 4/5级百分比、癌体积和术前血清前列腺特异性抗原水平后，这种风险降低消失了（风险比 = 1.03；95%置信区间，0.58 - 1.85）。总之，与Ff或FF基因型相比，ff基因型与侵袭性较小的组织病理学表现相关。有必要进行更大样本量的进一步研究，并调查FokI多态性在前列腺癌细胞中的功能意义。
