Genome-wide association study of prognosis in advanced non-small cell lung cancer patients receiving platinum-based chemotherapy.
Genome-wide association study of prognosis in advanced non-small cell lung cancer patients receiving platinum-based chemotherapy.
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DOI：
10.1158/1078-0432.ccr-12-1202
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发表时间：
2012-10-01
期刊：
影响因子：
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通讯作者：
Shen H
中科院分区：
文献类型：
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作者：
Hu L;Wu C;Zhao X;Heist R;Su L;Zhao Y;Han B;Cao S;Chu M;Dai J;Dong J;Shu Y;Xu L;Chen Y;Wang Y;Lu F;Jiang Y;Yu D;Chen H;Tan W;Ma H;Chen J;Jin G;Wu T;Lu D;Christiani DC;Lin D;Hu Z;Shen H
遗传变异可能影响癌症患者的化疗反应和总生存率。我们对来自两个独立队列（307例来自南京，228例来自北京）的535例晚期非小细胞肺癌（NSCLC）患者进行了全基因组扫描。对来自中国东南部的340名患者的独立队列进行了重复，然后对来自马萨诸塞州综合医院（Boston，MA）的409名患者进行了第二次验证。在中国人群中，5个单核苷酸多态性（SNP）与NSCLC生存率一致相关，在加性遗传模型中P值范围为3.63 × 10−5至4.19 × 10−7。3个SNPs的次要等位基因（3p22.1的rs7629386，5p14.1的rs 969088和14q24.3的rs3850370）与NSCLC生存率较差相关，而2个（7q31.31的rs 41997和9p21.3的rs 12000445）与NSCLC生存率较好相关。此外，3p22.1（CTNNB 1）和14q24.3（SNW 1-ALKBH 1-NRXN 3）的rs7629386在高加索人群中进一步复制。在这项三阶段全基因组关联研究中，我们确定了5个SNP作为中国汉族人群中接受一线铂类化疗的晚期NSCLC患者生存的标志物。其中两个SNP，rs7629386和rs3850370，也可能是高加索患者生存的标志物。
Genetic variation may influence chemotherapy response and overall survival in cancer patients. We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA). Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population. In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients.