Combinations of single nucleotide polymorphisms WWOX‐rs13338697, GALNT14‐rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced hepatocellular carcinoma. Issue 2 (11th July 2017) - Lin, Wey‐Ran
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.