BRCA1和BRCA2基因变异在结直肠癌中的表达特点与风险分析

Expression characteristics and risk analysis of BRCA1 and BRCA2 gene variants in colorectal cancer

目的探究结直肠癌发生、发展与BRCA1和BRCA2基因突变风险的关系。方法采用二代测序技术对2022年1月-2022年3月于首都医科大学附属北京友谊医院就诊的61例结直肠癌患者进行基因检测。收集患者发病年龄、性别、组织学分级、TNM分期等信息。根据BRCA1和BRCA2基因是否发生体系突变,将患者分为BRCA1和BRCA2基因体系突变组(n=8)和未突变组(n=53)。主要观察指标为结直肠癌的致病或可能致病性胚系突变基因与患者的临床病理资料的关系,包括发病年龄、性别、肿瘤发生部位、TNM分期、组织学分化、家族史。次要观察指标为结直肠癌患者BRCA1和BRCA2基因体系突变与患者临床病理资料的关系。正态分布的计量资料以均数±标准差(x±s)表示,组间比较采用t检验。非正态分布的计量资料以M(Q_(1),Q_(3))表示,组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ^(2)检验。结果在61例结直肠癌患者中,结直肠癌发生致病或可能致病的胚系突变频率为13.1%(8/61),其中BRCA1和BRCA2基因突变频率为3.3%(2/61)。BRCA1和BRCA2基因体系突变频率为13.1%(8/61),BRCA1和BRCA2基因体系突变组患者女性(75.0%比37.7%,χ^(2)=3.947,P=0.047)和右半结肠癌(75.0%比26.4%,χ^(2)=7.889,P=0.019)数量显著高于未突变组患者。结论结直肠癌患者BRCA1和BRCA2基因胚系和体系突变频率较高。具有乳腺癌或卵巢癌家族史结直肠癌患者BRCA1和BRCA2基因突变风险较大,推荐进行BRCA基因检测。

Objective To explore the relationship between the occurrence and development of colorectal cancer and the risk of BRCA1 and BRCA2 gene mutations.Methods Sixty-one patients with colorectal adenocarcinoma admitted to Beijing Friendship Hospital Affiliated to Capital Medical University from January 2022 to March 2022 were tested by second-generation sequencing.Information such as age of onset,gender,histological grade and TNM stage were collected.According to whether the BRCA1 and BRCA2 gene had systemic mutation,the patients were divided into BRCA1 and BRCA2 gene system mutation group and unmutated group.There were 8 cases in the BRCA1 and BRCA2 gene system mutant group and 53 cases in the non-mutant group.The main outcome measures were the relationship between pathogenic or likely pathogenic germline mutations in colorectal cancer and clinicopathological data of patients,including age of onset,gender,tumor location,TNM stage,histological differentiation,and family history.The secondary outcome was the relationship between BRCA1 and BRCA2 gene system mutations and clinicopathological data.Measurement data with normal distribution were expressed as mean±standard deviation(x±s),and comparison between groups was analyzed using the t-test.Measurement data with non-normal distribution were represented as M(Q_(1),Q_(3)),and comparison between groups was analyzed using the Mann-Whitney U test.Measurement data were expressed as the number of cases or percentage(%),and Chi-square test was used for comparison between groups.Results Among 61 colorectal adenocarcinoma patients,the frequency of pathogenic or potentially pathogenic germ line mutations in colorectal cancer was 13.1%(8/61),and the frequency of BRCA1 and BRCA2 mutations was 3.3%(2/61).The frequency of BRCA1 and BRCA2 mutations was 13.1%(8/61).Women with BRCA1 and BRCA2 mutations(75.0%vs 37.7%,χ^(2)=3.947,P=0.047)and right colon cancer(75.0%vs 26.4%,χ^(2)=7.889,P=0.019)were significantly higher than those without mutation.Conclusions The frequency of BRCA1 and BRCA2 gene mutation is higher in colorectal cancer patients.BRCA1 and BRCA2 gene mutations are recommended for colorectal cancer patients with a family history of breast or ovarian cancer.