天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (4): 389-393.doi: 10.11958/20150238

• 专题研究-乳腺肿瘤 • 上一篇    下一篇

C1236T、 G2677T/A 和C3435T 基因多态性与乳腺癌分子分型的关系及意义

刘新兰1 ， 张海霞2 ， 刘尧邦2 ， 姜敏3   

  1. 1宁夏医科大学总医院肿瘤医院肿瘤内科 （邮编750004）； 2宁夏医科大学临床医学院； 3宁夏医科大学总医院生物芯片中心
  • 收稿日期:2015-10-19 修回日期:2016-03-18 出版日期:2016-04-15 发布日期:2016-05-20
  • 作者简介:刘新兰 （1964）， 女， 硕士研究生， 主任医师， 教授， 主要从事肿瘤化疗相关研究
  • 基金资助:
    宁夏回族自治区高等学校科学研究项目 （NJ201050）

The correlation and significance of gene polymorphisms of C1236T, G2677T/A and C3435T with molecular subtypes of breast cancer

LIU Xinlan1 , ZHANG Haixia2 , LIU Yaobang2 , JIANG Min3   

  1. 1 General Hospital of Ningxia Medical University, Yinchuan 750004, China; 2 School of Clinical Medicine, Ningxia Medical University; 3 Department of Biochip Center, General Hospital of Ningxia Medical University
  • Received:2015-10-19 Revised:2016-03-18 Published:2016-04-15 Online:2016-05-20

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摘要： 摘要： 目的 观察多药耐药基因 1 （MDR1） 第 12、 21 及 26 外显子 C1236T、 G2677T/A 和 C3435T 基因多态性在乳腺癌患者外周血中的分布， 分析其与分子分型的关系。方法 应用高分辨熔解曲线 （HRM） 技术检测 400 例乳腺癌患者 C1236T、 G2677T/A 及 C3435T 基因多态性。采用 Hardy-Weinberg 遗传平衡检验进行基因型分布遗传平衡吻合度检验。参照 2013 年 St.Gallen 国际专家乳腺癌分子分型共识。分析乳腺癌患者中 C1236T、 G2677T/A 和 C3435T 基因型分布特点， 并探讨其与分子分型的关系。结果 （1）400 例乳腺癌患者中 C1236T、 G2677T/A 和 C3435T 中分别有 2 例、 3 例和 2 例标本未得出基因分型结果， C1236T 位点 CC、 CT 和 TT 基因型分别占 16.08% （64/398）、 44.22% （176/398） 和 39.70% （158/398）； G2677T/A 位点 GG、 GT、 GA、 TT 和 AT 基因型分别占 16.62% （66/397）、 44.33% （176/ 397）、 7.05% （28/397）、 27.46% （109/397） 和 4.54% （18/397）； C3435T 位点 CC、 CT 和 TT 基因型分别占 21.11% （84/ 398）、 56.03% （223/398） 和 22.86% （91/398）。经 Hardy-Weinberg 遗传平衡检验， 认为 C1236T、 G2677T/A 和 C3435T 基因多态性具有群体代表性 （P > 0.05）。（2） 分子分型显示， 11例人类表皮生长因子受体2 （HER-2， 2+） 患者未行荧光原位杂交 （FISH） 检测予以剔除， 其中Luminal A型占41.90% （163/389）， Luminal B型占32.65% （127/389）， HER-2过表达型占13.62% （53/389）， 三阴型占11.83% （46/389）。（3） C3435T位点CT/TT基因型在Luminal A型患者中的频率高于其在HER-2过表达型和三阴型患者中的频率 （χ2 =12.011， P=0.001； χ2 =13.976， P < 0.001）， C1236T和G2677T/A基因多态性在不同分子分型中的分布差异无统计学意义 （P > 0.05）。结论 MDR1基因C3435T位点多态性可以为乳腺癌异质性提供更合理的补充， 不同乳腺癌分子分型患者中CT/TT基因表型可能对药物治疗更敏感。

关键词: 乳腺肿瘤, 多态性, 单核苷酸, 高分辨熔解曲线技术, 分子分型, C1236T, G2677T/A, C3435T

Abstract: Abstract: Objective To investigate the distribution of the MDR1 exon12 (C1236T), exon21 (G2677T/A) and exon 26 (C3435T) gene polymorphisms in breast cancer patients, and to analyse their relationship with molecular subtypes of breast cancer. Methods The genotyping of C1236T, G2677T/A and C3435T were detected by polymerase chain reaction (PCR)- high resolution melting (HRM) method in 400 cases of breast cancer. The Hardy-Weinberg equilibrium test was used for ge⁃ netic equilibrium distribution of genotype. The molecular subtypes of breast cancer were classified based on St.Gallen Con⁃ sensus 2013. The genotype distributions of C1236T, G2677T/A and C3435T in breast cancer were analyzed. Their relation⁃ ship with molecular subtypes in breast cancer was analyzed as well. Results ① In 400 cases of breast cancer, there were 2, 3 and 2 specimens did not get genotyping results in C1236T, G2677T/A and C3435T genotype detection. The CC, CT and TT genotypes of C1236T accounted for 16.08% (64/398), 44.22% (176/398) and 39.70% (176/398). GG, GT, GA, TT and AT genotypes of G2677T/A accounted for 16.62% (66/397), 44.33% (176/397), 7.05% (28/397), 27.46% (109/397) and 4.54% (18/397). CC, CT and TT genotypes of C3435T accounted for 21.11% (84/398), 56.03% (223/398) and 22.86% (91/398) re⁃ spectively. Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T, G2677T/A and C3435T had group representation (P < 0.05). ② Eleven cases of HER-2 (2+) were excluded because they were not verified by FISH de⁃tection when performed molecular subtype of breast cancer. Luminal A subtype accounted for 41.90% (163/389), Luminal B subtype accounted for 32.65% (127/389), HER-2 over-expression subtype accounted for 13.62% (53/389) and triple negative subtype accounted for 11.83% (46/389). ③ CT/TT genotype frequency of C3435T was significantly higher in breast cancer patients with Luminal A subtype than that in breast cancer patients with HER-2 over-expression subtype and triple negative subtype (χ2 =12.011, P=0.001; χ2 =13.976, P < 0.001), while there was no statistical difference in C1236T and G2677T/ A gene polymorphism between different molecular subtypes of breast cancer (P > 0.05). Conclusion C3435T gene polymor⁃ phism can explain more accurately heterogeneity of breast cancer. CT/TT genotype in different molecular subtypes of breast cancer may be more sensitive to drug treatment.

Key words: breast neoplasms, polymorphism, single nucleotide, high resolution melting, molecular subtype, C1236T, G2677T/A, C3435T