UNASSIGNED: BRCA1 and BRCA2 are two highly penetrant genes involved in the inherited breast cancer and contribute to different DNA damage pathways and cell cycle and apoptosis cascades. Mutations in these genes have been associated with hypersensitivity and genetic instability as well as manifesting severe radiotherapy complications in breast cancer patients. The genomic instability and DNA repair capacity of breast cancer patients with BRCA1/2 mutations have been analyzed in different studies using a variety of assays, including micronucleus assay, comet assay, chromosomal assay, colony-forming assay, γ -H2AX and 53BP1 biomarkers, and fluorescence in situ hybridization. The majority of studies confirmed the enhanced spontaneous & radiation-induced radiosensitivity of breast cancer patients compared to healthy controls. Using G2 micronucleus assay and G2 chromosomal assay, most studies have reported the lymphocyte of healthy carriers with BRCA1 mutation are hypersensitive to invitro ionizing radiation compared to non-carriers without a history of breast cancer. However, it seems this approach is not likely to be useful to distinguish the BRCA carriers from non-carrier with familial history of breast cancer.
CONCLUSIONS: In overall, breast cancer patients are more radiosensitive compared to healthy control; however, inconsistent results exist about the ability of current radiosensitive techniques in screening BRCA1/2 carriers or those susceptible to radiotherapy complications. Therefore, developing further radiosensitivity assay is still warranted to evaluate the DNA repair capacity of individuals with BRCA1/2 mutations and serve as a predictive factor for increased risk of cancer mainly in the relatives of breast cancer patients. Moreover, it can provide more evidence about who is susceptible to manifest severe complication after radiotherapy.
■BRCA1和BRCA2是两个高度渗透的基因,与遗传性乳腺癌有关,并有助于不同的DNA损伤途径和细胞周期和凋亡级联反应。这些基因的突变与乳腺癌患者的超敏反应和遗传不稳定性以及表现出严重的放疗并发症有关。BRCA1/2突变的乳腺癌患者的基因组不稳定性和DNA修复能力已在不同的研究中使用各种检测方法进行了分析,包括微核试验,彗星试验,染色体分析,集落形成试验,γ-H2AX和53BP1生物标志物,和荧光原位杂交。大多数研究证实,与健康对照相比,乳腺癌患者的自发和辐射诱导的辐射敏感性增强。使用G2微核测定和G2染色体测定,大多数研究报道,与没有乳腺癌病史的非携带者相比,具有BRCA1突变的健康携带者的淋巴细胞对体外电离辐射过敏.然而,这种方法似乎不太可能用于区分BRCA携带者和有乳腺癌家族史的非携带者.
结论:总的来说,与健康对照相比,乳腺癌患者对放射更敏感;然而,关于目前的放射敏感技术筛查BRCA1/2携带者或易患放疗并发症者的能力,存在不一致的结果.因此,仍有必要开展进一步的放射敏感性试验,以评估BRCA1/2突变个体的DNA修复能力,并作为主要在乳腺癌患者亲属中增加癌症风险的预测因素.此外,它可以提供更多的证据,说明谁在放疗后容易出现严重并发症。