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. 2018 Apr;14(2):e54-e63.
doi: 10.1111/ajco.12745. Epub 2017 Jul 11.

Combinations of single nucleotide polymorphisms WWOX-rs13338697, GALNT14-rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced hepatocellular carcinoma

Wey-Ran Lin  1   2 , Chao-Wei Hsu  1   2 , Christopher Sung-Huan Yeh  3 , Yi-Cheng Chen  1   2 , Ming-Ling Chang  1   2 , Kung-Hao Liang  1 , Chen-Chun Lin  1 , Yu-De Chu  2 , Chau-Ting Yeh  1   2
Affiliations

Combinations of single nucleotide polymorphisms WWOX-rs13338697, GALNT14-rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced hepatocellular carcinoma

Wey-Ran Lin et al. Asia Pac J Clin Oncol. 2018 Apr.

Abstract

Aim: A genome-wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14-rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction.

Methods: A cohort of 116 HCC patients receiving split-dose chemotherapy composed of 5-fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14-rs9679162 together with four other leading candidate SNPs (rs6025211, rs715171, LOC105369482-rs1955024 and WWOX-rs13338697) was genotyped and correlated with time-to-tumor progression (TTP) and overall survival (OS).

Results: GALNT14-rs9679162-TT genotype remained an effective predictor for favorable TTP and OS (P = 0.012 and 0.002). Additionally, it was found that WWOX-rs13338697-CT genotype was associated with unfavorable TTP (P = 0.031), independent of GALNT14-rs9679162 genotype (adjusted P = 0.045), and rs6025211-CT genotype was associated with unfavorable OS (P = 0.014), independent of GALNT14-rs9679162 genotype (adjusted P = 0.025). Combinations of these SNPs stratified patients into three groups with differential treatment outcomes. Patients with GALNT14-rs9679162-TT/WWOX-rs13338697-non-CT genotypes achieved the most favorable treatment outcomes (n = 19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19 [21.1%], respectively); whereas patients with GALNT14-rs9679162-non-TT/rs6025211-CT genotypes associated with the most unfavorable treatment outcomes (n = 40; median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40 [2.5%], respectively). The remaining patients constituted a third subgroup with intermediate clinical outcomes.

Conclusions: Three genetic variants, GALNT14-rs9679162, WWOX-rs13338697 and rs6025211, stratified advanced HCC patients into three groups with differential treatment outcomes.

Keywords: chemotherapy; hepatocellular carcinoma; prognosis; single nucleotide polymorphism.

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