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Relationship between polymorphism of thymidylate synthase gene and side effects of FEC regimen for breast cancer patients of different races

ZHANG Feng-chun1,2, XU Hai-yan1, XU Guang-ru3, REN Fang1, MA Yue4, TANG Lei4, WANG Hong-xia4, XU Ying-chun4   

  1. 1.Department of Oncology, Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou 215021, China; 2.Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 3.Department of Oncology, Shanghai Pudong New Area People's Hospital, Shanghai 201200, China; 4.Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    Suzhou Science and Technology Program, SYS201062; Shanghai Pudong New Area Social Development Bureau Program, DW2007D-4; Science and Technology Foundation for Culture of Excellent Young Teachers in Shanghai, jdy09036


Objective To explore the distribution of polymorphism of thymidylate synthase (TYMS) gene in breast cancer patients and the relationship between the genotypes and the side effects of chemotherapy. Methods The variable number of tandem repeats (VNTR) in 28 bp of 5′untranslated region (untranslated region, 5′UTR) of TYMS gene was selected as the genetic marker. PCR-nondenaturing polyacrylamide gel electrophoresis was employed to determine the genotype of 50 Caucasian patients and 23 Asian patients with breast cancer and analysis was conducted according to clinical pathological features, side effects of FEC chemotherapy, and survival data of patients. Results The frequencies of genotypes of 2R/2R, 2R/3R, and 3R/3R of TYMS 28 bp VNTR in Caucasian patients were 12.0%, 62.0%, and 26.0%, and in Asian patients were 4.4%, 30.4%, 65.2%, respectively. The differences were statistically significant (P<0.05). The allclomorphic genes and genotypes of loci of TYMS 28 bp VNTR were irrelevant to histological types, histological grades, lymph node metastasis, clinical stages, estrogen receptor, progenstogen receptor, and human epidermal growth factor receptor 2. The mean time of follow-up was 43.21 months. Five cases relapsed and five patients died. The univariate analysis and multivariate analysis indicated that the genotype of TYMS gene was not a factor that affected the prognosis. After being treated by the chemotherapy, the incidence of leucopenia (grade 3-4) of Asian patients was significantly higher than that of Caucasian patients (86.96% vs 60.00%, P=0.021). The incidence of leucopenia (grade 3-4) of 3R/3R of TYMS 28 bp VNTR was higher than that of 2R/3R and 3R/3R. But the differences were not statistically significant (75.00%, 65.79%, and 57.14%, respectively, P=0.578). Conclusion The tolerability to FEC chemotherapy of Caucasian and Asian breast cancer patients is different. This may be relevant to the polymorphism of 28bp VNTR of TYMS gene.

Key words: breast cancer, thymidylate synthase gene, polymorphism, chemotherapy