汉族女性乳腺癌患者has-mir-125a-5p基因的rs12975333位点的单核苷酸多态性及其在癌组织的表达研究

Relationship between the single nucleotide polymorphisms in has-mir-125a-5p rs12975333 and expression of has-mir-125a-5p in Han Chinese female breast cancer patients

目的探讨汉族女性乳腺癌患者has-mir-125a-5p基因rs12975333化点单核盱酸多念性（SNP）及has-mir-125a-5p基因在癌组织表达水平与乳腺癌发生发展的关系。方法选取汉族女性乳腺癌患者289例、乳腺纤维腺瘤49例和相匹配的健康汉族妇女外周血338例，分离淋巴细胞，抽提基因组DNA，采用taqman—MGB探针检测338例乳腺肿瘤及338例健康对照组has-mir-125a-5p的rs12975333位点的单核苷酸多态性；采用茎环Real—timeRT—PCR检测289例乳腺癌组织及其正常腺体组织中has—mir-125a-5p的表达水平。结果乳腺癌组has—mir-125a-5p基因rs12975333位点基凶型为GG型273例（94．5％）、GT型16例（5．5％）；乳腺纤维腺瘤组及对照组has-mir-125a-5p基因rsl2975333位点基因型均为GG型；乳腺癌组织has-mir-125a-5p的表达水平（0．19±0．04）低于腺体组织（0．37±0．05），差异有统计学意义（P=0．04）；携带T等位基凶乳腺癌组织中has-mir-125a-5p下调水平较GG基因型表达者更为明显（P=0．022）。has-mir-125a-5p的表达降低在发病年龄较晚（P=0．036），ERBB2（P=0．007）、ERBB3（P=0．04）受体表达阴性及存在腋窝淋巴结转移（P=0．001）的乳腺癌组织中更为明显。结论汉族妇女has-mir-125a-5p丛因rs12975333位点的G〉T变异可能与乳腺癌遗传易感性有关；has-mir-125a-5p表达与乳腺癌发生发展相关，是一个潜在的乳腺癌分子标志物.

Objective To investigate the relationship between the single nucleotide polymorphisms （SNPs） in has-mir-125a-5p rs12975333 and the expression of has-mir-125a-Sp and clinicopathological cheracteristics of female breast cancer in Han Chinese women. Methods Genomic DNA was extracted from peripheral blood lymphocytes, taqman-MGB assay was used to type breast cancer of 338 cases and 338 controls. Expression levels of has-mir-125a-Sp in 289 biopsies were examined using stem-loop real-time RTPCR and the clinicopathological cheraeteristics of breast cancer were evaluated. Result The gene frequencies （GG,GT,TF） of rs12975333 in the patients were GG 273 （94. 5% ） , （,T 16 （5.5%） , TT 0（0%）, while in breast fibroadenoma and controls there were GG 49 （100%）, 338 （100%）. The expression level of has-mir-125a-Sp in breast cancer（0. 19 ± 0. 04） was lower than that in the matched non- tumor adjacent tissue specimens（0.37 ± 0. 05） （P = 0. 04）. The expression level of minor T allele of mature miR-125a in breast cancer patients was lower than that in ilas-mir-125a-Sp-GG carying（ P = 0. 022 ）. The expression of has-mir-125a-Sp was down-regulated in primary breast cancer, especially in ehter patients（ P = 0. 036） and lymph node metastasis groups （ P = 0. 001 ） and with negative ERBB2 （ P = 0. 007 ） , ERBB3 （P =0. 04）. Conclusions rs12975333 polyrnorphisms in has-mir-125a-Sp gene may work as a risk factor of breast cancer in Han Chinese women. The altered expression of has-mir-125a-5p might play a role in the pathogenesis and progression of breast carcinoma.