中国人群DBC2基因突变与乳腺癌的关系

The association between DBC2 gene mutation and breast cancer in Chinese population

目的:检测乳腺癌患者DBC2基因启动子和第7外显子及其两翼部分内含子区域的突变情况,探讨DBC2基因突变与乳腺癌发病风险的关系。方法:收集长海医院32例乳腺癌患者的组织标本,提取DNA后,对DBC2基因启动子、第7外显子及其侧翼部分内含子进行PCR扩增,通过直接测序法鉴定DNA突变位点。另取18例乳腺良性肿瘤组织标本作为对照。结果:研究组和对照组都没有发现启动子或第7外显子突变。在13例组织标本中发现DBC2第7内含子IVS7+53C>G突变,研究组和对照组的突变率分别为25.00%(8/32)和27.78%(5/18),2者差异无统计学意义(P>0.05)。IVS7+53C>G突变患者与野生型患者在年龄分布上差异无统计学意义(P>0.05)。DBC2基因IVS7+53C>G突变与肿瘤大小、淋巴结状态以及雌激素受体和孕激素受体表达与否等临床特征无统计学相关性(P>0.05)。但是IVS7+53C>G突变患者HER2和p53表达率显著高于野生型患者,提示IVS7+53C>G突变与HER2和p53表达相关(P<0.05)。结论:DBC2基因启动子及第7外显子突变可能在中国人群中并不常见,与乳腺癌发病风险无关。IVS7+53C>G突变是中国人群中一种常见的多态性,与乳腺癌发病风险的关系尚待今后更大样本量的研究予以论证。

Objective ： To investigate the prevalence of DBC2 gene mutations in its promoter, exon 7, and intron in the exon/ intron boundaries and explore the correlation of DBC2 mutation with the incidence of breast cancer. Methods ： DNA was extracted from 32 breast cancer specimens in Changhai Hospital. PCR was performed to amplify the sequence encoding the DBC2 gene promoter, exou 7, and intron in the exon/intron boundaries. The DNA mutation was identified by sequence analysis. Eighteen benign tumor specimens served as control cases. Results ： No mutation was found in the promoter and exon 7 in study group and control group. An intronic altera- tion （IVS7 ＋53C 〉 G） was found in 13 specimens. There was no significant difference in the IVS7 ＋53C 〉 G between study group and control group [ 25% （8/32） vs 27.78% （5/18）, P 〉 0.05 ]. The difference was not significant in age distribution between IVS7 ＋ 53C 〉 G mutation patients and wild type patients （P 〉0.05）. IVS7 ＋ 53C 〉 G mutation of DBC2 gene was not related with the tumor size, the lymph node metastasis, and expression of estrogen receptor or progesterone receptor （ P 〉 0.05 ）. The expressions of HER2 and p53 were significantly higher in IVS7 ＋ 53C 〉 G mutation patients than that in wild type patients indicating that IVS7 ＋ 53C 〉 G mu- tation was related with HER2 and p53 expressions （ P 〈 0.05 ）. Conclusion ： DBC2 gene mutations in the promoter and exou 7 were rare in Chinese population and may not contribute to the risk of breast cancer in China. The intronic alteration IVS7 ＋53C 〉 G was a common polymorphism in Chinese population, and further large sample test is required to reveal the relationship between IVS7 ＋ 53C 〉 G mutation and risk of breast cancer.