title: CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients.
abstract: BACKGROUND
  We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.
  
  
  METHODS
  Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).
  
  
  RESULTS
  Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.
  
  
  CONCLUSIONS
  Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.
authors.affiliation: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi, 410-769, Republic of Korea. sukryun73@hanmail.net
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kong
authors.forename: B-H
authors.initials: BH
authors.lastname: Nam
authors.forename: I J
authors.initials: IJ
authors.lastname: Choi
authors.forename: C G
authors.initials: CG
authors.lastname: Kim
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.forename: S J
authors.initials: SJ
authors.lastname: Cho
authors.forename: Y W
authors.initials: YW
authors.lastname: Kim
authors.forename: K W
authors.initials: KW
authors.lastname: Ryu
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Rhee
authors.forename: Y-I
authors.initials: YI
authors.lastname: Park
authors.forename: N K
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065637:Cytochrome P-450 CYP2A6; D004268:DNA-Binding Proteins / Q000235:genetics*; D004338:Drug Combinations; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D004338:Drug Combinations; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin