Kostovska I Maleva, Jakimovska M, Kubelka-Sabit K, Karadjozov M, Arsovski A, Stojanovska L, Plaseska-Karanfilska D
Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov," Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
"Adzibadem-Sistina" Hospital, Skopje, Republic of Macedonia.
Balkan J Med Genet. 2015 Dec 30;18(1):47-54. doi: 10.1515/bjmg-2015-0005. eCollection 2015 Jun.
Clinical importance of the most common CHEK2 (IVS2+1 G>A, 1100delC, I157T and del5395) and NBN (R215W and 657del5) gene mutations for breast cancer development in Macedonian breast cancer patients is unknown. We performed a case-control study including 300 Macedonian breast cancer patients and 283 Macedonian healthy controls. Genotyping was done using a fast and highly accurate single-nucleotide primer extension method for the detection of five mutations in a single reaction. The detection of the del5395 was performed using an allele-specific duplex polymerase chain reaction (PCR) assay. We have found that mutations were more frequent in breast cancer patients (n = 13, 4.3%) than in controls (n = 5, 1.8%), although without statistical significance. Twelve patients were heterozygous for one of the analyzed mutations, while one patient had two mutations (NBN R215W and CHEK2 I157T). The most frequent variant was I157T, found in 10 patients and four controls (p = 0.176) and was found to be associated with familial breast cancer (p = 0.041). CHEK2 1100delC and NBN 657del5 were each found in one patient and not in the control group. CHEK2 IVS2+1G>A and del5395 were not found in our cohort. Frequencies of the studied mutations are low and they are not likely to represent alleles of clinical importance in the Macedonian population.
在马其顿乳腺癌患者中，最常见的CHEK2（IVS2 +1 G>A、1100delC、I157T和del5395）和NBN（R215W和657del5）基因突变对乳腺癌发生发展的临床重要性尚不清楚。我们进行了一项病例对照研究，纳入300名马其顿乳腺癌患者和283名马其顿健康对照。采用快速且高度准确的单核苷酸引物延伸法进行基因分型，可在单个反应中检测5种突变。使用等位基因特异性双链聚合酶链反应（PCR）检测法检测del5395。我们发现，乳腺癌患者中的突变（n = 13，4.3%）比对照组（n = 5，1.8%）更常见，尽管无统计学意义。12名患者为其中一种分析突变的杂合子，而1名患者有两种突变（NBN R215W和CHEK2 I157T）。最常见的变异是I157T，在10名患者和4名对照中发现（p = 0.176），且发现与家族性乳腺癌相关（p = 0.041）。CHEK2 1100delC和NBN 657del5各在1名患者中发现，对照组未发现。CHEK2 IVS2 +1G>A和del5395在我们的队列中未发现。所研究突变的频率较低，在马其顿人群中它们不太可能代表具有临床重要性的等位基因。
