BACKGROUND: Genetic variations influence treatment outcomes in cancer patients treated with chemotherapy. Detection of pharmacogenetic markers associated with treatment response may enable doctor to plan more precise and effective treatment tailoring to individual cancer patients. METHODS: A novel oligonucleotide microarray was developed to genotype 13 variations (DPYD*2, DPYD*5, DPYD*9, TYMS 6 bp Ins/Del, UGT1A1*6, UGT1A1*27, UGT1A1*28, GSTP1 Ile105Val, XRCC1 Arg399Gln, MTHFR C677T, MDR1 C3435T/A, MDR1 G2677A/T and ERCC1 C118T). The accuracy of genotypes obtained by microarray was assessed by independent sequencing. 73 patients first diagnosed with colorectal cancer (CRC) were treated with FOLFOX4 chemotherapy. RESULTS: All genotypes were successfully called by microarray, and were consistent with those identified by independent sequencing except two TYMS 6 bp Ins/Del genotypes. Patients with CT or TT genotype exhibited a higher probability of response to treatment than those with CC genotype. No other SNP was found to be associated with treatment response. Furthermore, these SNPs showed no associations with gastrointestinal, hematological or neurological toxicity. CONCLUSIONS: ERCC1 C118T may be a predictive marker of treatment response to 5-FU/platinum chemotherapy for CRC. The microarray can significantly facilitate the process of detecting genetic variations and may help doctor plan more effective medication for individual cancer patient.
BACKGROUND: Genetic variations influence treatment outcomes in cancerpatients treated with chemotherapy. Detection of pharmacogenetic markers associated with treatment response may enable doctor to plan more precise and effective treatment tailoring to individual cancerpatients. METHODS: A novel oligonucleotide microarray was developed to genotype 13 variations (DPYD*2, DPYD*5, DPYD*9, TYMS 6 bp Ins/Del, UGT1A1*6, UGT1A1*27, UGT1A1*28, GSTP1Ile105Val, XRCC1 Arg399Gln, MTHFRC677T, MDR1C3435T/A, MDR1G2677A/T and ERCC1C118T). The accuracy of genotypes obtained by microarray was assessed by independent sequencing. 73 patients first diagnosed with colorectal cancer (CRC) were treated with FOLFOX4 chemotherapy. RESULTS: All genotypes were successfully called by microarray, and were consistent with those identified by independent sequencing except two TYMS 6 bp Ins/Del genotypes. Patients with CT or TT genotype exhibited a higher probability of response to treatment than those with CC genotype. No other SNP was found to be associated with treatment response. Furthermore, these SNPs showed no associations with gastrointestinal, hematological or neurological toxicity. CONCLUSIONS:ERCC1C118T may be a predictive marker of treatment response to 5-FU/platinum chemotherapy for CRC. The microarray can significantly facilitate the process of detecting genetic variations and may help doctor plan more effective medication for individual cancerpatient.
Entities:
Keywords:
5-FU; ERCC1; Single nucleotide polymorphism; drug response; molecular biomarker; platinum
Authors: Maarten J Deenen; Jolien Tol; Artur M Burylo; Valerie D Doodeman; Anthonius de Boer; Andrew Vincent; Henk-Jan Guchelaar; Paul H M Smits; Jos H Beijnen; Cornelis J A Punt; Jan H M Schellens; Annemieke Cats Journal: Clin Cancer Res Date: 2011-04-15 Impact factor: 12.531
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