title: Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer.
abstract: BACKGROUND
  Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.
  
  
  METHODS
  One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.
  
  
  RESULTS
  Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.
  
  
  CONCLUSIONS
  GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.
authors.affiliation: Center of Breast Diseases and Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Bao-Ning
authors.initials: BN
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Zheng
authors.forename: Ning
authors.initials: N
authors.lastname: Lü
authors.forename: Bing-He
authors.initials: BH
authors.lastname: Xu
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Guo-Ji
authors.initials: GJ
authors.lastname: Chen
authors.forename: Dian-Ke
authors.initials: DK
authors.lastname: Yu
authors.forename: Dong-Xin
authors.initials: DX
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015251:Epirubicin; D003520:Cyclophosphamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi