Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Wenzhou 325035, PR China.
BMC Med Genet. 2009 Dec 4;10:125. doi: 10.1186/1471-2350-10-125.
Molecular epidemiological studies have shown that gene polymorphisms of vitamin D receptor (VDR) are associated with prostate cancer risks. However, previous results from many molecular studies remain inconsistent.
Blood samples were collected from 122 prostate cancer patients and 130 age-matched control subjects in the Han population of Southern China. The differences of VDR gene polymorphism between cancer cases and controls were determined by PCR-RFLP, examiming FokI (exon 2), BsmI, Tru9I, ApaI (intron 9), and TaqI (exon 9). Associations between the VDR gene polymorphism and prostate cancer risk were calculated in an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software.
Of five polymorphisms, BsmI was shown to associate with prostate cancer, while FokI, Tru9I, ApaI, and TaqI did not show any significant association. After adjustment for age, the BsmI 'B' allele was associated with an almost 1/3-fold risk (OR = 0.35, 95%CI: 0.15-0.80) of the occurrence of prostate cancer, a 1/5-fold risk (OR = 0.20, 95%CI: 0.06-0.68) of poorly differentiated prostate cancer, and a 1/10-fold risk (OR = 0.10, 95%CI: 0.01-0.78) of aggressive prostate cancer compared with the 'b' allele, especially among older men (>71 years). In addition, haplotype analysis revealed that the 'F-b-U-A-T' was more frequent found in cases than in controls (3.4% vs 0.0%, P = 0.0035), while the frequency of haplotype 'F-B-U-a-T' was 0.8% in cases, significantly lower than in controls (3.9%, P = 0.019).
Our experiments provide evidences that genetic polymorphisms in the VDR gene may be potential risk factors for prostate cancer in the Han population of southern China and the susceptibility to prostate cancer is associated with ethnicity and geographic location.
分子流行病学研究表明,维生素 D 受体(VDR)基因多态性与前列腺癌风险相关。然而,来自许多分子研究的先前结果仍然不一致。
采集中国南方汉族人群中 122 例前列腺癌患者和 130 例年龄匹配的对照者的血样。通过 PCR-RFLP 检测 VDR 基因多态性,检测 FokI(外显子 2)、BsmI、Tru9I、ApaI(内含子 9)和 TaqI(外显子 9)的差异。采用非条件 logistic 回归模型计算 VDR 基因多态性与前列腺癌风险的关系。采用 SHEsis 软件分析连锁不平衡和单倍型。
在五种多态性中,BsmI 与前列腺癌相关,而 FokI、Tru9I、ApaI 和 TaqI 与前列腺癌无关。在调整年龄后,BsmI‘B’等位基因与前列腺癌的发生风险几乎降低了 1/3(OR=0.35,95%CI:0.15-0.80),低分化前列腺癌的发生风险降低了 1/5(OR=0.20,95%CI:0.06-0.68),侵袭性前列腺癌的发生风险降低了 1/10(OR=0.10,95%CI:0.01-0.78),与‘b’等位基因相比,特别是在年龄较大的男性(>71 岁)中。此外,单体型分析显示,‘F-b-U-A-T’在病例中比在对照中更常见(3.4%对 0.0%,P=0.0035),而‘F-B-U-a-T’单体型的频率在病例中为 0.8%,明显低于对照(3.9%,P=0.019)。
本实验提供的证据表明,VDR 基因的遗传多态性可能是中国南方汉族人群前列腺癌的潜在危险因素,且前列腺癌的易感性与种族和地理位置有关。