Abstract | AIM: MATERIALS & METHODS: This study was conducted in two steps. First, a genome-wide retrospective screen was performed in a cohort of 16 patients. A candidate SNP marker was identified as being associated with the objective responses to the first course of FMP. Second, a validation of this candidate SNP was performed prospectively in an independent cohort of 41 patients. The survival curves were also compared in patient subgroups stratified by the SNP marker. RESULTS: The genome-wide screening revealed several candidate markers, including seven adjacent SNPs residing in a 5-kb linkage disequilibrium block and in an intronic region of GALNT14 on chromosome 2. Among them, the SNP rs9679162 manifested the strongest association when genotypic tests and kernel-based association tests were performed. Significant association was found again between rs9679162 and the therapeutic responses in the validation cohort (p = 0.006326). A follow-up survival analysis demonstrated that patients with a homozygous rs9679162 genotype had better progression-free survival in both the retrospective and prospective cohorts (p = 0.00041 and 0.01485, respectively) than the other genotypes did. However, the overall survival curve is only different in the retrospective cohort (p = 0.00622) and not in the prospective cohort. CONCLUSION:
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Authors | Kung-Hao Liang, Chen-Chun Lin, Chau-Ting Yeh |
Journal | Pharmacogenomics
(Pharmacogenomics)
Vol. 12
Issue 7
Pg. 1061-73
(Jul 2011)
ISSN: 1744-8042 [Electronic] England |
PMID | 21635146
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers, Pharmacological
- Mitoxantrone
- N-Acetylgalactosaminyltransferases
- UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human
- Cisplatin
- Fluorouracil
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Biomarkers, Pharmacological
- Carcinoma, Hepatocellular
(drug therapy, mortality)
- Cisplatin
(administration & dosage)
- Disease-Free Survival
- Female
- Fluorouracil
(administration & dosage)
- Genome-Wide Association Study
- Humans
- Linkage Disequilibrium
- Liver Neoplasms
(drug therapy, mortality)
- Male
- Middle Aged
- Mitoxantrone
(administration & dosage)
- N-Acetylgalactosaminyltransferases
(genetics)
- Neoplasm Staging
- Polymorphism, Single Nucleotide
- Prospective Studies
- Retrospective Studies
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