Bcl-2基因多态性与乳腺癌临床生物学指标的关系

Correlation of Bcl-2 polymorphism with clinical biological behaviors of breast cancer

目的：探讨凋亡基因Bcl-2启动子区C（-938）A单核苷酸多态性（snigle nucleotide polymorphism,SNP）与河北省乳腺癌患者临床生物学指标的关系。方法：采用聚合酶链反应-限制性酶切片段长度多态性分析（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）方法检测113例乳腺癌患者Bcl-2基因C（-938）A SNP的3个基因型（即AA、AC和CC）,并与临床生物学指标相关联,比较各组间基因型频率的分布情况。结果：按腋淋巴结转移个数进行分层分析,AA型和AC＋CC型在无转移、1~3个转移、≥4个转移组中分别占26.8%、47.8%、52.6%和73.2%、52.2%、47.4%,两组比较差异有统计学意义（χ2=6.337,P=0.042）;与AC＋CC型相比,AA型在≥4个转移组OR值为3.041（95%CI：1.072~8.626）。在组织学分级中,AA型和AC＋CC型在Ⅰ~Ⅱ级、Ⅲ级中分别占30.9%、57.9%和69.1%、42.1%,两组基因型分布差异有统计学意义（χ2=5.055,P=0.025）;与AC＋CC型相比,AA型在肿瘤分化Ⅲ级组中OR值为3.082（95%CI：1.122~8.465）。按雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）和C-erbB2蛋白表达水平进行分层分析,发现AA型和AC＋CC型的上述指标分布差异无统计学意义（χ2=3.005,χ2=1.504,χ2=1.163;P〉0.05）。结论：乳腺癌患者Bcl-2基因C（-938）A SNP的AA基因型与其腋淋巴结转移率较高和肿瘤组织分化较差相关。

Objective：To study the correlation of C（-938）A single nucleotide polymorphism（SNP） in the promoter of anti-apoptosis gene Bcl-2 with the clinical biological parameters of breast cancer patients in Hebei Province.Methods：Three genotypes（AA,AC,CC） of Bcl-2 C（-938）A from 113 samples of breast cancer patients were analyzed by using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method,and the results were associated with clinical biological parameters.The distribution of genotype frequency was compared between different groups.Results：When stratified for axillary lymph node metastases,the frequency of AA genotype were 26.8%,47.8% and 52.6% and the distribution of AC＋CC genotypes were 73.2%,52.2% and 47.4% in negative group,1-3 metastasis group,and ≥4 metastasis group.The difference between the two groups was significant（χ2=6.337,P=0.042）.Compared with the AC＋CC genotypes,the OR value of AA genotype in ≥4 metastasis group was 3.041（95%CI=1.072-8.626）.The frequency of AA genotype were 30.9% and 69.1% in gradeⅠ-Ⅱ group and grade Ⅲ group,and the frequency of AC＋CC genotypes were 57.9% and 42.1%.The difference between the two groups was significant（χ2=5.055;P=0.025）.Compared with the AC＋CC genotypes,the OR value of AA genotype in differentiated tumors（grade Ⅲ）was 3.082（95%CI=1.122-8.465）.Stratified for estrogen receptor（ER）,progesterone receptor（PR） and C-erbB2,there was no difference between the distribution of AA genotype and AC＋CC genotypes（χ2=3.005,χ2=1.504,χ2=1.163,P0.05）.Conclusion：The AA genotype of Bcl-2 gene C（-938）A maybe correlated with high lymph node metastasis rate and poor differentiation.