Genome-wide association study on platinum-induced hepatotoxicity in non-small cell lung cancer patients

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 patientsâ (tm) 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.