Suspitsin Evgeny N, Sherina Nathalia Yu, Ponomariova Daria N, Sokolenko Anna P, Iyevleva Aglaya G, Gorodnova Tatyana V, Zaitseva Olga A, Yatsuk Olga S, Togo Alexandr V, Tkachenko Nathalia N, Shiyanov Grigory A, Lobeiko Oksana S, Krylova Nadezhda Yu, Matsko Dmitry E, Maximov Sergey Ya, Urmancheyeva Adel F, Porhanova Nathalia V, Imyanitov Evgeny N
Laboratory of Molecular Oncology, N,N, Petrov Institute of Oncology, St, Petersburg, Russia.
Hered Cancer Clin Pract. 2009 Feb 25;7(1):5. doi: 10.1186/1897-4287-7-5.
A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.
The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.
BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.
Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.
相当一部分卵巢癌（OC）病例是由BRCA1或BRCA2基因的种系突变引起的。在具有奠基者效应的人群中，BRCA检测成本低廉，因此建议对所有确诊为OC的患者进行检测。在俄罗斯，复发性突变构成了BRCA缺陷的绝大多数，然而其对OC发病率的影响尚未得到系统研究。此外，俄罗斯人群的特点是CHEK2和NBS1（NBN）杂合子频率相对较高，但尚不清楚这两个基因是否会增加OC风险。
该研究纳入了来自两个不同的、地理位置偏远地区的354例OC患者（290例来自俄罗斯西北部（圣彼得堡），64例来自该国南部（克拉斯诺达尔））。通过等位基因特异性PCR检测DNA样本中8种奠基者突变（BRCA1 5382insC、BRCA1 4153delA、BRCA1 185delAG、BRCA1 300T>G、BRCA2 6174delT、CHEK2 1100delC、CHEK2 IVS2+1G>A、NBS1 657del5）的存在情况。此外，还回顾了关于非选择性OC患者中BRCA1、BRCA2、CHEK2和NBS1突变发生情况的文献数据。
在来自俄罗斯西北部的28/290（9.7%）例OC病例和来自俄罗斯南部的11/64（17.2%）例OC患者中检测到BRCA1 5382insC等位基因。此外，还检测到4例BRCA1 185delAG、2例BRCA1 4153delA、1例BRCA2 6174delT、2例CHEK2 1100delC和1例NBS1 657del5突变。克拉斯诺达尔的1例患者同时为BRCA1 5382insC和NBS1 657del5变异的杂合子。
奠基者BRCA1突变，尤其是BRCA1 5382insC变异，在俄罗斯OC发病率中占相当大的比例，因此对于每一位俄罗斯裔OC患者都应考虑进行DNA检测。结合文献数据，本研究不支持CHEK2对OC风险有影响，而NBS1杂合子的作用可能需要进一步阐明。
