CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in patients with non-small-cell lung cancer.
CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C), CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected among Chinese that may influence the efficacy of vinorelbine-based therapies to treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of 32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of 27 (22.22%) of those heterozygous (C/T) at this site responded. (chi2=5.68, p < 0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous (G/G) responded (chi2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated with response to vinorelbine. No significant difference in toxicity and survival was observed according to SNP genotype.
Pan
Ji-Hong
JH
Key Laboratory of Ministry of Health for Biotech-Drug, Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, 89 Jingshi Road, Jinan, Shandong Province, 250062, China.
Han
Jin-Xiang
JX
Wu
Jian-Mei
JM
Sheng
Li-Jun
LJ
Huang
Hai-Nan
HN
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002681:China / Q000453:epidemiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000187:drug effects*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects; D011237:Predictive Value of Tests; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D000077235:Vinorelbine