A sequence polymorphism on 8q24 is associated with survival in hepatocellular carcinoma patients who received radiation therapy

Xiao-Mei Zhao,Ping Yang,Yi-Xing Chen,Yong Hu,Zuo-Lin Xiang,Zhao-Chong Zeng

doi:10.1038/s41598-018-20700-x

Abstract

There is a growing consensus that genetic variation in candidate genes can influence cancer progression and treatment effects. In this study, we genotyped the rs9642880 G > T polymorphism using DNA isolated from blood samples of 271 hepatocellular carcinoma (HCC) patients who received radiotherapy treatment. We found that patients who carried the GT or TT genotypes had significantly shorter median survival times (MSTs) compared to patients with the GG genotype (14.6 vs.21.4 months). The multivariate P value was 0.027, the hazard ratio (HR) was 1.38, and the 95% confidence interval was 1.04–1.84. Further analysis revealed that patients with the variant genotypes had an increased risk of poor tumour response to radiotherapy (P = 0.036 and 0.002 for stable disease and progressive disease, respectively) and higher incidence of multiple intrahepatic lesions (P = 0.026) and BCLC C stage (P = 0.027). Moreover, further stratified survival analyses revealed that at least radioresponse and BCLC stage contributed to the association between the rs9642880 G > T polymorphism and survival of HCC patients in this study (P value, 0.017 vs 0.053 for BCLC C stage vs B stage; 0.011 vs 0.531 for radioresponse SD + PD vs CR + PR). These results illustrate the potential association between rs9642880 G > T and survival in HCC patients who received radiotherapy treatment.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common liver malignancies, and its incidence is increasing in most parts of the world
We investigated the associations between the c-MYC rs9642880 G > T polymorphism on 8q24 and survival in 271 hepatocellular carcinoma (HCC) patients following radiotherapy treatment
We found that the presence of at least one T allele was significantly associated with an unfavourable survival outcome for HCC patients following radiation therapy

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common liver malignancies, and its incidence is increasing in most parts of the world. Surgical resection is the most common treatment choice for HCC, but for a considerable number of cases, surgical resection is not suitable because of factors such as large tumour size, concomitant liver cirrhosis, or portal vein tumour thrombosis. In these inoperable HCC cases, radiotherapy can be an effective treatment option[1,2]. The overexpression of c-MYC is considered to be associated with promoting radioresistance in nasopharyngeal carcinomas[9]; we hypothesize that the c-MYC rs9642880 G > T polymorphism is associated with the survival of HCC patients who received radiation therapy. Variables Age (y) Average median Gender Male Female KPS 100 90 80 AFP

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Results

Conclusion