A single nucleotide polymorphism on the GALNT14 gene as an effective predictor of response to chemotherapy in advanced hepatocellular carcinoma.

Abstract

Previously, a pilot genome-wide association study has identified candidate single nucleotide polymorphism predictors for the therapeutic response of 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy in advanced hepatocellular carcinoma (HCC). Here, we conducted a prospective confirmatory study to examine the predictive value of rs9679162 (located on GALNT14 gene) for the therapeutic responses using a split-dose FMP protocol. One hundred and seven advanced HCC patients receiving split-dose FMP therapy were enrolled. All patients were in Barcelona Clinical Liver Cancer Stage C with either main portal vein thrombosis and/or distant metastasis. Of them, 105 (98.1%) were Child-Pugh classification B. GALNT14 genotype was determined before therapy. Of the patients included, 28 were rs9679162 "TT" and 79 were "non-TT" ("GG" + "GT") genotype. The median overall survival, time-to-progression, response rate and disease control rate were ("TT" versus "non-TT") 6.8 versus 3.9 months (p < 0.001), 3.9 versus 2.1 months (p < 0.001), 28.6% versus 10.1% (p = 0.029) and 35.7% versus 15.2% (p = 0.030), respectively. Multivariate analysis indicated that rs9679162 genotype was an independent predictor for overall survival (p = 0.002). Categorical analysis showed that 17 patients with "TT" genotype, tumor size < 10 cm and neutrophils < 74% had a median overall survival of 25.5 months and a therapeutic response rate of 47.1%. In conclusion, this prospective study confirmed that GALN14 genotype (rs9679162) was an effective predictor for therapeutic outcome in advanced HCC patients treated by FMP chemotherapy. Combining GALNT14 genotype and clinical parameters, a subgroup of patients with excellent outcome was identified.

• Authors: Chau-Ting Yeh, Kung-Hao Liang, Chen-Chun Lin, Ming-Ling Chang, Cheng-Lung Hsu, Chien-Fu Hung
• Journal: International journal of cancer (Int J Cancer) Vol. 134 Issue 5 Pg. 1214-24 (Mar 01 2014) ISSN: 1097-0215 [Electronic] United States
• PMID: 23959947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 UICC.

Chemical References

• Mitomycin
• N-Acetylgalactosaminyltransferases
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, genetics, mortality)
• Cisplatin (therapeutic use)
• Female
• Fluorouracil (therapeutic use)
• Genotype
• Humans
• Liver Neoplasms (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Mitomycin (therapeutic use)
• N-Acetylgalactosaminyltransferases (genetics)
• Neutropenia (epidemiology)
• Polymorphism, Single Nucleotide
• Prospective Studies