The State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Pharmacogenet Genomics. 2010 Jun;20(6):389-95. doi: 10.1097/FPC.0b013e32833a6890.
Small-cell lung cancer (SCLC) accounts for about 20% of total lung cancer, and systemic chemotherapy is the major therapy for all stages of SCLC. Although most SCLC patients are characterized by initial chemosensitivity to the standard first-line platinum-based regimens, a significant fraction of patients are intrinsic nonresponders.
Genome-wide scan of 440 093 single-nucleotide polymorphisms (SNPs) was conducted using peripheral blood DNA to identify variants associated with response to first-line carboplatin or cisplatin plus etoposide chemotherapy in 245 patients with SCLC and the results were replicated in another set of 183 patients.
By set association analysis, 20 SNPs were identified to be associated with treatment response, with odds ratios (95% confidence interval) ranging from 2.36 (1.56-3.57) to 4.38 (2.12-9.29) and these results were confirmed in the replication phase. Most of these SNPs (14/20) were clustered on chromosomes 22p11.23, 6q24.3, and 20p12.2 containing BTBD3, STXBP5, and BCR genes.
Germline genetic variations influence the effectiveness of platinum-based chemotherapy of SCLC and further studies are needed to test the value of these findings for personalized chemotherapy.
小细胞肺癌（SCLC）约占肺癌总数的 20%，所有阶段的 SCLC 主要治疗方法均为全身化疗。虽然大多数 SCLC 患者对标准一线含铂方案的化疗最初具有敏感性，但仍有相当一部分患者属于内在耐药者。
使用外周血 DNA 进行了 440093 个单核苷酸多态性（SNP）的全基因组扫描，以鉴定与 245 例 SCLC 患者一线卡铂或顺铂加依托泊苷化疗反应相关的变体，并在另一组 183 例患者中进行了验证。
通过集联分析，鉴定出 20 个与治疗反应相关的 SNP，其比值比（95%置信区间）范围为 2.36（1.56-3.57）至 4.38（2.12-9.29），这些结果在验证阶段得到了确认。这些 SNP 中的大多数（14/20）位于包含 BTBD3、STXBP5 和 BCR 基因的染色体 22p11.23、6q24.3 和 20p12.2 上。
种系遗传变异影响 SCLC 基于铂类化疗的有效性，需要进一步研究来检验这些发现对个体化化疗的价值。
