title: Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer.
abstract: OBJECTIVE
  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: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-Dong, 110-744 Chongno-Gu, Seoul, Korea.
authors: Kyung-Hun
authors: KH
authors: Lee
authors: Hye Jung
authors: HJ
authors: Chang
authors: Sae-Won
authors: SW
authors: Han
authors: Do-Youn
authors: DY
authors: Oh
authors: Seock-Ah
authors: SA
authors: Im
authors: Yung-Jue
authors: YJ
authors: Bang
authors: Sun Young
authors: SY
authors: Kim
authors: Keun-Wook
authors: KW
authors: Lee
authors: Jee Hyun
authors: JH
authors: Kim
authors: Yong Sang
authors: YS
authors: Hong
authors: Tae Won
authors: TW
authors: Kim
authors: Young Suk
authors: YS
authors: Park
authors: Won Ki
authors: WK
authors: Kang
authors: Sang Joon
authors: SJ
authors: Shin
authors: Joong Bae
authors: JB
authors: Ahn
authors: Gyeong Hoon
authors: GH
authors: Kang
authors: Seung-Yong
authors: SY
authors: Jeong
authors: Kyu Joo
authors: KJ
authors: Park
authors: Jae-Gahb
authors: JG
authors: Park
authors: Tae-You
authors: TY
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D007723:Korea; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: C000715087:ABCC2 protein, human; D004268:DNA-Binding Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002955:Leucovorin; D005472:Fluorouracil