Abstract 807: Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients
Authors: Yeung Chun Philip , Chong Ching Ning Charing , Cheung Tan To , Ng Kelvin Kwok Chai , Lai Paul Bo San , Cheung Siu Tim 
Published: July 2021

Abstract
Background/Aims Incidence of HCC varies in diverse localities with differences on ethnicity and risk factors. The majority of HCC cases worldwide are from China, thus raising the concern on genetic susceptibility in addition to the prevalence of hepatitis virus infection. Drug transporter ABCB5 has been reported to be overexpressed in HCC and associated with poor survival. Recently a panel of SNPs and INDELs in ABCB5 gene have been reported to associate with HCC risk (Leung et al. 2020). We aim to further examine the ethnic differences on the ABCB5 genetic variations between local cohort and the data from The 1000 Genome Project.
Subjects and Methods 300 HCC and 300 healthy blood samples were prospectively collected with informed consent. All patients had been diagnosed with primary HCC and underwent partial hepatectomy. Clinical information including sex, age, tumor stage and survival outcomes were collected prospectively. Genomic DNA were extracted from blood samples and SNPs were examined. SNP allele frequencies in different populations were obtained from The 1000 Genomes Browser by NCBI.
Results Twelve ABCB5 genetic variants were within the coding regions, with one splicing variant, one stop codon change, while 2 were synonymous and 8 were non-synonymous changes. In particular, allele frequencies of rs2074000 observed in healthy local cohorts (C: 0.517 vs A: 0.483) were comparable to East Asian, while the genetic variation was absent in European in 1000 Genomes Project (CHB - C: 0.534 vs A: 0.466; CHS - C: 0.548 vs A: 0.452; GBR - C: 1.000 vs A: 0.000; CEU - C: 1.000 vs A: 0.000; P&lt;0.001). Similarly, allele frequencies of rs17143187 in healthy local cohorts (G: 0.518 vs C: 0.482) were comparable to East Asian (CHB - G: 0.539 vs C: 0.461; CHS - G: 0.567 vs C: 0.433), while it was absent among European (GBR and CEU - G: 1.000 vs C: 0.000) (P&lt;0.001). Data from our local HCC cohorts further demonstrated that rs2074000 and rs17143187 were independent protective factors in overall survival (Cox HR; rs2074000: 0.676, 95% CI: 0.49-0.93, P=0.017; rs17143187: 0.709, 95% CI: 0.51-0.98, P=0.038). These ABCB5 genetic variants were associated with early tumor stage (OR; rs2074000: 0.351, 95% CI: 0.21-0.59, P&lt;0.001; rs17143187: 0.382, 95% CI: 0.22-0.65, P&lt;0.001) and solitary tumor nodule (OR; rs2074000: 0.507, 95% CI: 0.30-0.86, P=0.012; rs17143187: 0.517, 95% CI: 0.30-0.88, P=0.015).
Conclusions ABCB5 genetic variants rs2074000 and rs17143187 mainly prevalent in East Asian predicted better overall survival among HCC patients. ABCB5 is crucial in tumor-initiating cells in melanoma. ABCB5 rs2074000 (non-synonymous SNP, Gln to Lys, classified as damaging by SIFT score) and rs17143187 (splicing variant) both predicted to confer non-functional proteins, thus partly explain the protective effects. Further functional studies are warranted to comprehend the underlying mechanisms.
Citation Format: Chun Philip Yeung, Ching Ning Charing Chong, Tan To Cheung, Kelvin Kwok Chai Ng, Paul Bo San Lai, Siu Tim Cheung. Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 807.