Dogan Irem, Onen Hacer Ilke, Yurdakul Ahmet Selim, Konac Ece, Ozturk Can, Varol Ayhan, Ekmekci Abdullah
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
Med Sci Monit. 2009 Aug;15(8):BR232-42.
Differences between the individual variations in DNA may modulate lung cancer process. Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms may influence the cancer risk due to their antiproliferative, antiangiogenic, antimetastatic and apoptotic effects.
MATERIAL/METHODS: The genotype and haplotype frequencies of three polymorphisms of VDR, i.e. TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), were studied using PCR-RFLP in 137 patients with lung cancer and 156 controls.
Differences were observed in genotype (P=0.024) and allele (P=0.011) frequencies of TaqI polymorphism due to the "T" allele. Furthermore, compared with the "tt" genotype, the odds ratio for the "TT" genotype increased 2.24 times (95%CI=1.05-4.77, P=0.037). Comparing cases and controls, smoking habit (P=0.012) and gender distribution (P=0.005) were found to increase the risk of lung cancer in patients with "TT" homozygotes, demonstrating the role of gene-environment interaction in lung cancer. In addition, when age and gender within the case group only were evaluated in relation to genotype, the adjusted odds ratios for the "TT" genotype increased 2.20 times (95%CI=1.01-4.78, P=0.047) for age and 2.24 times (95%CI=1.05-4.80, P=0.037) for gender. However, no differences were observed for the distribution of variant genotypes of the BsmI and ApaI polymorphisms (P>0.05). To evaluate the joint effects of these polymorphisms, haplotype analysis was performed which showed that the haplotype baT was associated with higher lung cancer risk compared with the most common haplotype BAt (P=0.026).
This is perhaps the first study suggesting that TaqI polymorphism of the VDR gene might be a risk factor for lung cancer and that age, gender, and smoking habit could have an impact on lung cancer risk.
DNA个体差异可能会调节肺癌进程。许多研究报告称，维生素D受体（VDR）基因多态性因其抗增殖、抗血管生成、抗转移和凋亡作用，可能会影响癌症风险。
材料/方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对137例肺癌患者和156例对照者的VDR基因的三种多态性，即TaqI（rs731236）、BsmI（rs1544410）和ApaI（rs7975232）的基因型和单倍型频率进行了研究。
由于“T”等位基因，TaqI多态性的基因型（P=0.024）和等位基因（P=0.011）频率存在差异。此外，与“tt”基因型相比，“TT”基因型的优势比增加了2.24倍（95%置信区间=1.05-4.77，P=0.037）。比较病例组和对照组发现，吸烟习惯（P=0.012）和性别分布（P=0.005）会增加“TT”纯合子患者患肺癌的风险，表明基因-环境相互作用在肺癌中的作用。此外，仅在病例组内按年龄和性别评估基因型时，“TT”基因型的校正优势比在年龄方面增加了2.20倍（95%置信区间=1.01-4.78，P=0.047），在性别方面增加了2.24倍（95%置信区间=1.05-4.80，P=0.037）。然而，BsmI和ApaI多态性的变异基因型分布没有差异（P>0.05）。为了评估这些多态性的联合效应，进行了单倍型分析，结果表明，与最常见的单倍型BAt相比，单倍型baT与更高的肺癌风险相关（P=0.026）。
这可能是第一项表明VDR基因的TaqI多态性可能是肺癌危险因素，且年龄、性别和吸烟习惯可能会影响肺癌风险的研究。
