Wang Na-na, Wang Jian-ye, Shi Xiao-hong, Zhang Yao-guang, Liu Ming, Wang Xin, Hui Juan, Chen Xin, Liang Si-ying, Wei Dong, Yang Fan, Zhao Fan, Zhang Yu-hong, Yang Ze
Institute of Geriatrics, Beijing Hospital, Ministry of Health of PR China, Beijing 100730, China.
Zhonghua Zhong Liu Za Zhi. 2013 Apr;35(4):262-7. doi: 10.3760/cma.j.issn.0253-3766.2013.04.005.
To explore the association between the common variations of TET2 (rs7679673, A), MTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes and prostate cancer (Pca) risk in Chinese population in Beijing, and to understand the relationship between genotypes and phenotypes including clinical characteristics and life style, etc. in patients with prostate cancer.
Based on a case-control study, 124 patients with prostate cancer and 138 age-matched control subjects were recruited. Information of clinical phenotype and life style, etc. in the prostate cancer patients was collected. We compared the differences of allele and genotype frequencies of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) gene expressions between the two groups for the allele and genotype frequencies, and explored the relationship between different genotypes and clinical features such as patient age, BMI, Gleason score, PSA level and tumor stage, by Chi-square test in patients with PCa. Multifactor dimensionality reduction was used to detect the gene-gene interactions.
The FAM84B (rs12543663, C) C carriers frequency had significant difference between the case group and the control group (χ(2) = 3.980 P = 0.046; OR = 1.883; 95%CI = 1.006-3.526). The allele and genotype frequencies of TET2 gene (rs7679673, A) and LMTK2 gene (rs6465657, T) were not significantly different between the case group and the control group (P > 0.05). Analysis of the genotypes and clinical phenotypes showed that the genetic type of FAM84B C carriers [CX (CC + CA)] were significantly associated with cancer stage (χ(2) = 9.585; P = 0.002; OR = 3.740; 95%CI = 1.580 - 8.853). Association between three loci and 12 kind of relevant outcomes was found in TET2 A carriers and the smoking and drinking patients (all P < 0.05). Significant correlation was also found between LMTK2 (rs6465657, T) TX carriers and surgery (χ(2) = 8.612; P = 0.003; OR = 0.174; 95%CI 0.049 - 0.620). No significant correlation was seen with other covariates (P > 0.05). Dendrogram analysis among the three loci showed that the best model consisted of the three sites (P = 0.0270), cross validation consistency: 10/10, and testing balanced accuracy: 0.5120. There may be gene-gene interaction among TET2 (rs7679673, A), LMTK2 (rs6465657, T), and FAM84B (rs12543663, C).
There may be obvious association of FAM84B (rs12543663, C) gene with prostate cancer risk and the stages, and the synergistic effects of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes may have an association with prostate cancer risk in Chinese population.
探讨TET2基因（rs7679673，A）、MTK2基因（rs6465657，T）和FAM84B基因（rs12543663，C）的常见变异与北京中国人群前列腺癌（Pca）风险之间的关联，并了解前列腺癌患者的基因型与包括临床特征和生活方式等在内的表型之间的关系。
基于一项病例对照研究，招募了124例前列腺癌患者和138例年龄匹配的对照受试者。收集前列腺癌患者的临床表型和生活方式等信息。我们比较了两组之间TET2基因（rs7679673，A）、LMTK2基因（rs6465657，T）和FAM84B基因（rs12543663，C）表达的等位基因和基因型频率的差异，并通过卡方检验探讨前列腺癌患者中不同基因型与患者年龄、BMI、Gleason评分、PSA水平和肿瘤分期等临床特征之间的关系。采用多因素降维法检测基因-基因相互作用。
FAM84B基因（rs12543663，C）的C携带者频率在病例组和对照组之间存在显著差异（χ(2)=3.980，P=0.046；OR=1.883；95%CI=1.006-3.526）。TET2基因（rs7679673，A）和LMTK基因（rs6465657，T）的等位基因和基因型频率在病例组和对照组之间无显著差异（P>0.05）。对基因型和临床表型的分析表明，FAM84B基因C携带者[CX（CC+CA）]的基因型与癌症分期显著相关（χ(2)=9.585；P=0.002；OR=3.740；95%CI=1.580-8.853）。在TET2基因A携带者与吸烟和饮酒患者中发现三个位点与12种相关结局之间存在关联（均P<0.05）。还发现LMTK2基因（rs6465657，T）的TX携带者与手术之间存在显著相关性（χ(2)=8.612；P=0.003；OR=0.174；95%CI 0.049-0.620）。与其他协变量无显著相关性（P>0.05）。对三个位点的聚类分析表明，最佳模型由这三个位点组成（P=0.0270），交叉验证一致性：10/10，测试平衡准确率：0.5120。TET2基因（rs7679673，A）、LMTK2基因（rs6465657，T）和FAM84B基因（rs12543663，C）之间可能存在基因-基因相互作用。
FAM84B基因（rs12543663，C）与前列腺癌风险及分期可能存在明显关联，TET2基因（rs7679673，A）、LMTK2基因（rs6465657，T）和FAM84B基因（rs12543663，C）的协同作用可能与中国人群前列腺癌风险有关。
