title: MGMT -535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy.
abstract: OBJECTIVE
  The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.
  
  
  METHODS
  A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR-RFLP assay.
  
  
  RESULTS
  During the median follow-up duration of 15.9 (2.1-53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) -535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423-6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101-6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P < 0.001 and 0.001, respectively).
  
  
  CONCLUSIONS
  The MGMT -535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Nung Soo
authors.initials: NS
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Byung Woog
authors.initials: BW
authors.lastname: Kang
authors.forename: Hun Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Bae
authors.forename: Gyu Seog
authors.initials: GS
authors.lastname: Choi
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Jun
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015254:DNA Modification Methylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D025521:Tumor Suppressor Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D005472:Fluorouracil