摘要
目的探讨瘦素受体(LEPR)基因表达及其多态性与乳腺癌发生、发展及病理学特征之问的关系。方法采用免疫组织化学法和聚合酶链反应.限制性片段长度多态(PCR.RFLP)分析技术,对150例乳腺癌患者肿瘤组织、80例乳腺良性病变患者病变组织、50例患者癌旁正常乳腺组织和128例健康对照者静脉血进行LEPR基因表达及Gln223Arg多态性检测。结果LEPR在乳腺癌组织中表达的阳性率为70.67%(106/150),高于乳腺良性病变组的56.25%(45/80)和癌旁正常组织组的44.00%(22/50)(均P〈0.005)。LEPR基因Gln223Arg的GG、C.A、AA基因型在乳腺癌组的分布频率分别为70.00%(105例)、16.67%(25例)和13.33%(20例),在良性病变组为82.5%(66例)、13.75%(11例)、3.75%(3例),在癌旁正常组织组为82.00%(41例)、14.00%(7例)、4.00%(2例),在健康对照组为82.8l%(106例)、14.85%(19例)和2.34%(3例),三组比较差异有统计学意义(x。=11.56,P=0.003),GG、GA、AA基因型在乳腺良性疾病组、癌旁正常组织组和健康对照组分布频率比较,差异无统计学意义(P〉0.05)。乳腺癌组G和A等位基因分布频率分别为78.33%(235例)和21.67%(65例),与良性病变组、癌旁正常组织组及健康对照组相比,差异有统计学意义(x2=12.52,P=0.001)。LEPR基因在淋巴结转移患者中阳性表达率为87.8%,高于无淋巴结转移患者的60.2%,差异有统计学意义(P=0.02)。多因素分析表明,LEPR基因高表达、Gln223Arg多态性及腰臀比(WHR)升高是乳腺癌发生的危险因素(均OR〉I)。结论LEPR高表达、Gln223Arg多态性及WHR升高可能增7JI-~L腺癌发生的风险。
Objective To evaluate the association of expressions and gene polymorphism of leptin receptor (LEPR) in breast cancer with tumorigenesis, development and clinicopathologic factors. Methods The immunohistochemical method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to evaluate LEPR expressions and LEPR Gln223Arg polymorphism in 150 cases with breast cancer, 80 eases with benign breast lesions, 50 cases with corresponding normal breast tissue and 128 healthy controls. Results The expression rate of LEPR genes in breast cancer tissues was significantly higher than that in benign breast lesions and that in corresponding normal breast tissues [70.67 % (106/150) vs 56.25 % (45/80) vs 44.00 % (22/50), P 〈 0.005]. In breast cancer patients, LEPR gene Gin223Arg genotype polymorphism (GG, GA and AA) frequencies were 70.00 % (105 cases), 16.67 % (25 cases) and 13.33 % (20 cases), which were significantly different from those in the benign breast lesions [82.50 % (66 cases), 13.75 % (11 cases), 3.75 % (3 cases)], those in corresponding normal breast tissues [82.00 % (41 cases), 14.00 % (7 cases), 4.00 % (2 cases)] or those in the health controls [82.81% (106 cases), 14.85 % (19 cases) and 2.34 % (3 cases)] (x2 = 11.56, P = 0.003), while the differences of GG, GA and AA genotype requencies among the breast benign disease group, cancer adjacent normal breast group and healthy control group were not statistically significant (P 〉 0.05). The frequencies of alleles genes in breast cancer patients (G and A) were 78.33 % (235 cases) and 21.67 % (65 cases), and the differences were statistically significant compared with those in the benign disease group or in healthy control group (x2 = 12.52, P = 0.001). The positive expression rate of LEPR gene in patients with lymph node metastasis was 87.8 %, which was higher than that in patients with no lymph node metastasis (60.2 %) (P = 0.02). According to the results of multivariable analyses, high expression of LEPR gene, LEPR Gin223Arg gene polymorphisms and increased waist-hip ratio (WHR) were risk factors for breast cancer (all OR 〉 1). Conclusion High expression of LEPR, LEPR Gln233Arg polymorphism and the elevated WHR may be correlated with breast cancer.
出处
《肿瘤研究与临床》
CAS
2015年第11期740-744,共5页
Cancer Research and Clinic
基金
山西省自然科学基金(2006011129)
关键词
乳腺肿瘤
瘦素受体
基因
多态性
单核苷酸
Breast neoplasms
Leptin receptor
Genes
Polymorphism, single nucleotide