Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese.
Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese.
复制标题
PP2A 亚基基因的功能性遗传多态性导致中国南部和东部地区患肺癌的风险增加
DOI：
10.1371/journal.pone.0077285
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Yang R;Yang L;Qiu F;Zhang L;Wang H;Yang X;Deng J;Fang W;Zhou Y;Lu J
蛋白磷酸酶 -2A（PP2A）是细胞内主要的丝氨酸 - 苏氨酸磷酸酶之一，作为一种肿瘤抑制因子，对某些致癌激酶的活性起负调控作用。近期研究报道，在肺癌发生过程中PP2A的表达受到抑制，因此我们假设PP2A亚基基因中的单核苷酸多态性（SNP）可能影响PP2A的功能，进而导致肺癌易感性。在一项包含1559例肺癌患者和1679例对照的两阶段病例对照研究中，我们对中国南方和东部人群中7个主要PP2A亚基（即PPP2R1A、PPP2R1B、PPP2CA、PPP2R2A、PPP2R2B、PPP2R5C、PPP2R5E）中的8个推定功能性SNP和1个已确定的功能性SNP（即rs11453459）进行了基因分型。我们发现，PPP2R1A的rs11453459G（-G/GG）变异基因型和PPP2R5E的rs1255722AA变异基因型增加了患肺癌的风险（rs11453459，-G/GG与 - 相比：优势比（OR）=1.31，95%置信区间（CI）=1.13 - 1.51；rs1255722，AA与AG/GG相比：OR = 1.27，95% CI = 1.07 - 1.51）。将这两个变异联合分析后，不良基因型的数量与肺癌风险呈剂量反应关系（趋势P = 5.63×10⁻⁶）。进一步的功能分析表明，携带rs1255722AA变异基因型的肺癌组织，其PPP2R5E的mRNA水平显著低于携带GG/GA基因型的组织。然而，其他SNP及其他组合未观察到这种效应。我们的研究结果表明，PPP2R1A和PPP2R5E中的这两个功能性变异及其组合与中国人群的肺癌风险相关，可能是预测肺癌风险的有价值生物标志物。
Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases and functions as a tumor suppressor that negatively regulates the activity of some oncogenic kinases. Recent studies have reported that PP2A expression was suppressed during lung carcinogenesis, we there hypothesized that the single nucleotide polymorphisms (SNPs) in PP2A subunit genes may affect PP2A function and thus contribute to lung cancer susceptibility. In a two-stage case-control study with a total of 1559 lung cancer patients and 1679 controls, we genotyped eight putative functional SNPs and one identified functional SNP (i.e., rs11453459) in seven major PP2A subunits (i.e., PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E) in southern and eastern Chinese. We found that rs11453459G (-G/GG) variant genotypes of PPP2R1A and the rs1255722AA variant genotype of PPP2R5E conferred increased risks of lung cancer (rs11453459, -G/GG vs. –: OR = 1.31, 95% CI = 1.13–1.51; rs1255722, AA vs. AG/GG: OR = 1.27, 95% CI = 1.07–1.51). After combined the two variants, the number of the adverse genotypes was positively associated with lung cancer risk in a dose-response manner (P trend = 5.63×10−6). Further functional assay showed that lung cancer tissues carrying rs1255722AA variant genotype had a significantly lower mRNA level of PPP2R5E compared with tissues carrying GG/GA genotypes. However, such effect was not observed for the other SNPs and other combinations. Our findings suggested that the two functional variants in PPP2R1A and PPP2R5E and their combination are associated with lung cancer risk in Chinese, which may be valuable biomarkers to predict risk of lung cancer.
登录
查看更多内容
影响因子：
1.9
作者：
Cheng Y;Liu W;Kim ST;Sun J;Lu L;Sun J;Zheng SL;Isaacs WB;Xu J
通讯作者：
Xu J
影响因子：
6.2
作者：
Dupont, William D.;Breyer, Joan P.;Bradley, Kevin M.;Schuyler, Peggy A.;Plummer, W. Dale;Sanders, Melinda E.;Page, David L.;Smith, Jeffrey R.
通讯作者：
Smith, Jeffrey R.
DOI：
10.1016/s0197-2456(98)00037-3
发表时间：
1998-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Dupont, WD;Plummer, WD
通讯作者：
Plummer, WD
关联分析确定了中国人群中多个新的肺癌易感位点及其与吸烟的相互作用
影响因子：
30.8
作者：
Dong J;Hu Z;Wu C;Guo H;Zhou B;Lv J;Lu D;Chen K;Shi Y;Chu M;Wang C;Zhang R;Dai J;Jiang Y;Cao S;Qin Z;Yu D;Ma H;Jin G;Gong J;Sun C;Zhao X;Yin Z;Yang L;Li Z;Deng Q;Wang J;Wu W;Zheng H;Zhou G;Chen H;Guan P;Peng Z;Chen Y;Shu Y;Xu L;Liu X;Liu L;Xu P;Han B;Bai C;Zhao Y;Zhang H;Yan Y;Amos CI;Chen F;Tan W;Jin L;Wu T;Lin D;Shen H
通讯作者：
Shen H
影响因子：
3.7
作者：
Chen HG;Han WJ;Deng M;Qin J;Yuan D;Liu JP;Xiao L;Gong L;Liang S;Zhang J;Liu Y;Li DW
通讯作者：
Li DW