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Genome-wide Association Study on Platinum-induced Hepatotoxicity in Non-Small Cell Lung Cancer Patients

Songyu Cao,Cheng Wang,Hongxia Ma,R. Yin,Meng Zhu,W. Shen,J. Dai,Y. Shu,Lin Xu,Zhibin Hu,Hongbing Shen

Published 2015 in Scientific Reports

ABSTRACT

Platinum-based chemotherapy has been shown to improve the survival of advanced non-small cell lung cancer (NSCLC) patients; the platinum-induced toxicity severely impedes the success of chemotherapy. Genetic variations, such as single nucleotide polymorphisms (SNPs), may contribute to patients’ responses to the platinum-based chemotherapy. To identify SNPs that modify the risk of hepatotoxicity in NSCLC patients receiving platinum-based chemotherapy, we performed a genome-wide association scan in 334 subjects followed by a replication study among 375 subjects. Consistent associations with platinum-induced hepatotoxicity risk was identified for SNP rs2838566 located at 21q22.3, as the minor A allele could significantly increase the risk of liver injury (OR = 3.78, 95%CI = 1.99–7.19, P = 4.90 × 10−5 for GWAS scan, OR = 1.89, 95%CI = 1.03–3.46, P = 0.039 for replication and OR = 2.56, 95%CI = 1.65–3.95, P = 2.55 × 10−5 for pooled population). These results suggested that genetic variants at 21q22.3 may contribute to the susceptibility of platinum-induced hepatotoxicity in NSCLC patients.

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