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Mao, Chenxue; Chen, Juan; Zou, Ting; Zhou, Yuankang; Liu, Junyan; Li, Xi; Li, Xiangping; Li, Min; Pan, Pinhua; Zhuo, Wei; Gao, Yang; Hu, Shuo; Xiao, Desheng; Wu, Lin; Wang, Zhan; Xu, Heng; Yang, Wen; Xu, Yingjie; Xiao, Haihua; Hanada, Kazuhiko; Zhang, Wei; Zhou, Honghao; Yin, Jiye; Liu, Zhaoqian
Acta pharmaceutica Sinica. B, 03/2022, Letnik: 12, Številka: 3Journal Article
To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10−3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10−4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients. This study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients. Display omitted
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in: SICRIS
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