Genome-wide examination of genetic variants associated with response to platinum-based chemotherapy in patients with small-cell lung cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wu
Chen
C
The State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Xu
Binghe
B
Yuan
Peng
P
Ott
Jurg
J
Guan
Yin
Y
Liu
Yu
Y
Liu
Zhe
Z
Shen
Yuanyuan
Y
Yu
Dianke
D
Lin
Dongxin
D
D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005796:Genes; D016678:Genome; D006801:Humans; D004930:Inuit / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010984:Platinum / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D050683:R-SNARE Proteins; D055752:Small Cell Lung Carcinoma
D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; C484767:STXBP5 protein, human; D010984:Platinum; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin