上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

胸苷酸合成酶基因多态性与不同种族乳腺癌FEC方案化疗不良反应相关性研究

张凤春1,2，徐海燕1，徐光如3, 任 芳1, 马 越4，唐 雷4，王红霞4，徐迎春4   

  1. 1.上海交通大学 医学院附属苏州九龙医院肿瘤科， 苏州 215021； 2.上海交通大学 医学院附属瑞金医院肿瘤科， 上海 200025； 3.上海市浦东新区人民医院肿瘤科, 上海 201200； 4.上海交通大学 医学院附属仁济医院肿瘤科， 上海 200127
  • 出版日期:2014-06-28 发布日期:2014-06-30
  • 通讯作者: 徐迎春, 电子信箱: xiaoxu2384@163.com; 唐 雷, 电子信箱: bobbytang_1982@163.com。
  • 作者简介:张凤春（1957—）， 男， 主任医师， 博士， 博士生导师; 电子信箱: fczhang2004@163.com。
  • 基金资助:

    苏州市科技计划项目(SYS201062)；上海市浦东新区社会发展局卫生科技项目（DW2007D-4）；上海高校选拔培养优秀青年教师科研专项基金资助项目(jdy09036)

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

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摘要：

目的 了解胸苷酸合成酶基因（TYMS）多态性在乳腺癌患者中的分布及其基因型与化疗不良反应的关系。方法 选取雌激素受体基因5′端非编码区的28 bp串联重复序列（VNTR）作为遗传标记，运用PCR-聚丙烯酰胺凝胶电泳分析法对50例白种人和23例亚裔乳腺癌患者进行基因分型，结合患者临床病理特征、FEC化疗不良反应和生存数据进行分析。结果 TYMS 28 bp VNTR 基因型在白种人群2R/2R、2R/3R和3R/3R的基因型频率分别为12.0%、62.0%和26.0%，在亚裔人群分别为4.4%、30.4%和65.2%，差异有统计学意义（P<0.05）。TYMS 28 bp VNTR位点的等位基因及基因型与患者组织学类型、组织学分级、淋巴结转移、临床分期、雌激素受体、孕激素受体和人类表皮生长因子受体-2表达等无关。所有患者平均随访时间43.21个月，复发5例，死亡5例；单因素及多因素分析提示TYMS基因型不是影响预后因素。亚裔人群化疗后3-4级白细胞减少症发生率显著高于白种人群（86.96% vs 60.00%，P=0.021）；TYMS 28 bp VNTR 3R/3R基因型中，3-4级白细胞减少症发生率高于2R/3R、2R/2R，但差异无统计学意义（75.00% vs 65.79%，57.14%，P=0.578）。结论 白种人与亚裔乳腺癌患者FEC化疗耐受性存在差异，可能与两者TYMS基因28 bp VNTR多态性差异有关。

关键词: 乳腺癌, 胸苷酸合成酶基因, 多态性, 化疗

Abstract:

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