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Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer.
MedLine Citation:
PMID:  23314736     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy. METHODS: We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer. RESULTS: In contrast to previous studies in Caucasians, neutropenia (grade 3-4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19-4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20-17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2-4 neuropathy [adjusted OR 0.52, 95 % CI 0.27-0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS 'low' genotype (adjusted HR 1.83, 95 % CI 1.003-3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms. CONCLUSIONS: Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.
Authors:
Kyung-Hun Lee; Hye Jung Chang; Sae-Won Han; Do-Youn Oh; Seock-Ah Im; Yung-Jue Bang; Sun Young Kim; Keun-Wook Lee; Jee Hyun Kim; Yong Sang Hong; Tae Won Kim; Young Suk Park; Won Ki Kang; Sang Joon Shin; Joong Bae Ahn; Gyeong Hoon Kang; Seung-Yong Jeong; Kyu Joo Park; Jae-Gahb Park; Tae-You Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-13
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  -     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-Dong, 110-744, Chongno-Gu, Seoul, Korea.
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