BRCA1基因突变与乳腺癌易感性及其乳腺癌分型特征的关联分析

A Molecular Epidemiology Study on the Association of BRCA1 Mutations and the Susceptibility and Typing of Breast Cancer

目的研究BRCA1基因特定外显子位点突变与乳腺癌发病年龄、早发性和三阴性的相关性。方法对纳入的172例散发性乳腺癌患者外周血进行DNA提取,并对患者BRCA1基因第2、10、11 3个外显子突变高频区域进行基因测序。应用统计学分析,对BRCA1基因位点突变同乳腺癌分型进行关联分析。结果 172例患者中发现15例BRCA1基因突变患者,12个突变位点,基因突变频率为8.72%。12个突变位点中2号外显子1个(162A>G),10号外显子4个(1227G>A、2238T>C、2309G>A及2798T>C),11号外显子7个(1504delTTAAA、2201C>T、2731T>C、3232A>G、3449insA、3537A>G及3667A>G)。此外,早发性乳腺癌患者BRCA1突变率7.87%,非早发性乳腺癌患者突变率2.41%,两者之间无显著性差异(χ~2=2.578,P=0.108)。BRCA1基因突变患者平均年龄(43.73±4.90)岁,显著低于无突变组(51.12±5.13岁)(P=0.021)。三阴性乳腺癌患者BRCA1突变率为14.29%,显著高于非三阴性乳腺癌患者的5.50%突变率,两者之间存在统计学差异(χ~2=3.867,P=0.049)。结论 BRCA1基因突变患者年龄低,且基因突变与三阴性乳腺癌相关。

Objective To study the correlation among the mutation of BRCA1 gene specific exon sites and age of onset,early-onset breast cancer,and triple-negative breast cancer. Methods DNA was extracted from peripheral blood of 172 patients with sporadic breast cancer and the genes were sequenced in the high frequency regions of 2,10 and 11 of BRCA1 gene.Statistical analysis was used to analyze the association of BRCA1 gene mutation with breast cancer typing. Results In this study,15 cases of BRCA1 mutations with 12 mutation sites were found,and the frequency of BRCA1 mutation was 8.72%.There were one mutation in exon 2 (162 A >G),four mutations in exon 10 (1227 G >A、2238T >C、2309 G >A and 2798 T >C),and seven mutations in exon 11 (1504 delTTAAA、2201 C >T、2731T >C、3232 A >G、3449 insA、3537 A >G and 3667 A >G).In addition,the rate of BRCA1 mutation in early-onset breast cancer was 7.87%,and the mutation rate was 2.41% in non-early-onset breast cancer patients.There was no significant difference between the two groups (χ 2=2.578, P =0.108).The mean age of BRCA1 mutations was (43.73±4.90) years,which was lower significantly than that of the non-mutant group (51.12±5.13)( P = 0.021 ).14.29% of BRCA1 mutant group were diagnosed as triple-negative breast cancer,and the diagnostic rate of BRCA1 non-mutant group was 5.50%,and there was significant difference between the two groups (χ 2=3.867, P =0.049). Conclusion Triple-negative breast cancer arising in young people was correlated with BRCA1 gene mutation.