乳腺癌患者胸苷酸合成酶基因多态性及其与临床病理的关系

目的 研究胸苷酸合成酶(thymidylate synthase,TS)基因多态性在汉族女性乳腺癌患者中的分布特点及其与临床病理之间的关系.方法收集经病理学确诊的83例初诊乳腺癌患者外周静脉血,术前均未给予任何针对乳腺癌的治疗,应用聚合酶链反应限制性片段长度多态性技术(PCR-RFLP)检测墓因型.基因多态性与临床病理的关系采用卡方分析进行检验.结果 83例乳腺癌患者的基因分布情况为:(1)3R/3R、2R/3R及2R/2R 3种基因型的频率分别为68.7%、27.7%、3.6%;(2)按G→C单核苷酸多态性细分,2R/2R,2R/3C,2R/3G,3G/3G,3C/3C及3G/3C 6种基因型的频率分别为3.6%、19.3%、8.4%、19.3%、37.3%及12.1%;(3)+/+6 bp、+/-6 bp及-/-6 bp3种基因型的频率分别为8.4%、50.6%及41.0%;(4)3种基因多态性均与乳腺癌的组织学分级相关(P＜0.05);另外TS 5′-UTR多态性与淋巴结转移(P=0.019)、Ki67(P=0.022)相关,TS 3′-UTR多态性与发病年龄相关(P=0.002),G→C单核苷酸多态性与淋巴结转移相关(P=0.021).结论 汉族女性乳腺癌患者中3R/3R、-/-6 bp基因型频率较高;TS基因多态性与乳腺癌临床病理因素密切相关.

A study on the thethymidylate synthase gene polymorphisms and its relationship with clinical characteristics in breast cancer

Objective To investigate the distribution of thethymidylate synthase (TS) gene polymorphisms in Chinese female Han-nationality breast cancer patients, including tandem repeat polymorphisms in the enhancer region ( ER), 6 bp deletion/insertion (del6/ins6) polymorphism in the 3′untranslated region (3′-UTR) and G→C single-nucleotide polymorphism (SNP). The association of TS gene polymorphism with pathological results was retrospectively analyzed. Methods This study included 83 breast cancer patients who received no preoperative chemotherapy. The polymorphisms of TS, ER and TS 3′2UTR were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Results ( 1 ) Of the 83 patients, the frequencies of the TSER 3R/3 R, 2R/3 R and 2R/2R were 68.7％ ,27. 7％ and 3. 6％, respectively; (2) Due to existence of the G→C single nucleotide polymorphism,TSER genotypes were divided into 2R/2R, 2R/3C, 2R/3G, 3G/3G,3C/3C and 3G/3C,their frequencies were 3. 6％, 19. 3％, 8.4％, 19. 3％, 37. 3％ and 12. 1％, respectively; ( 3 ) Of the 83 patients, the frequencies of the TS 3′-UTR ins6/ias6、ins6/del6 and del6/del6 were 8.4％ 、50.6％ and 41.0％, respectively; (4) TSER polymorphisms were correlated with lymph node metastasis ( P = 0.019 ),Ki67 ( P = 0.022 ) and histological grade ( P = 0.042 ). The TS 3′-UTR polymorphisms were correlated with age ( P = 0.002) and histological grade (P = 0.042). G→C SNP were correlated with lymph node metastasis ( P = 0.021 ) and histological grade ( P = 0.028 ). Conclusions Chinese female Han-nationality breast cancer patients have more genotypes frequencies of the TSER 3R/3R and 3′-UTR del6/del6; The TS polymorphisms are correlated with pathological factors of breast cancer.