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Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

Cited 32 time in Web of Science Cited 36 time in Scopus
Authors
Lee, Kyung-Hun; Chang, Hye Jung; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue; Kim, Sun Young; Lee, Keun-Wook; Kim, Jee Hyun; Hong, Yong Sang; Kim, Tae Won; Park, Young Suk; Kang, Won Ki; Shin, Sang Joon; Ahn, Joong Bae; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Park, Jae-Gahb; Kim, Tae-You
Issue Date
2013-04
Citation
Cancer Chemotherapy and Pharmacology, Vol.71 No.4, pp.843-851
Keywords
Adjuvant chemotherapyColon cancerOxaliplatinPolymorphismToxicity
Abstract
Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy. 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. 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. 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.
ISSN
0344-5704
URI
https://hdl.handle.net/10371/173021
DOI
https://doi.org/10.1007/s00280-013-2075-3
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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