Abulkhair Omalkhair, Al Balwi Mohammed, Makram Ola, Alsubaie Lamia, Faris Medhat, Shehata Hussam, Hashim Ahmed, Arun Banu, Saadeddin Ahmed, Ibrahim Ezzeldin
Omalkhair Abulkhair, Specialized Medical Center; Mohammed Al Balwi, Ola Makram, Lamia Alsubaie, Hussam Shehata, Ahmed Hashim, and Ahmed Saadeddin, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs; Mohammed Al Balwi, King Abdullah International Medical Research Center, Ministry of National Guard-Health Affairs; Mohammed Al Balwi, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh; Medhat Faris, King Fahad Specialist Hospital, Dammam; Ezzeldin Ibrahim, Oncology Center of Excellence, International Medical Center, Jeddah, Kingdom of Saudi Arabia; and Banu Arun, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Glob Oncol. 2018 Aug;4:1-9. doi: 10.1200/JGO.18.00066.
Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations. Results Of 310 patients, 270 (87%) had no mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were found in 11% of patients, and BRCA2 mutations were found in 2% of patients. Variants of unknown significance were found in 15% of patients (45 patients). Triple-negative BC (TNBC) accounted for 86% of all patients with BC and mutations. The following three recurrent deleterious founder BRCA1 mutations were observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC was observed in three unrelated patients, and c.4524G>A mutations were observed in five unrelated patients. One novel mutation was identified in the BRCA1 gene (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype. Furthermore, age alone does not have a significant association with mutation, but a combination of risk factors such as age, familial history, and TNBC has a significant association with BRCA mutation.
目的 在过去三十年中，阿拉伯女性乳腺癌（BC）的发病率持续上升。然而，关于BRCA1/2突变患病率的数据却很稀少。尽管沙特阿拉伯的人口总体上具有同质性，近亲结婚很常见，尤其是在该国的中部、东部和南部地区，但该国BRCA1和BRCA2突变的患病率以及BC的特征尚未得到充分研究。方法 这项前瞻性观察性研究旨在确定BRCA1和BRCA2突变的患病率，并试图研究与这些突变相关的BC的临床病理特征。结果 在310例患者中，270例（87%）没有突变。在40例患者中发现了BRCA突变；11%的患者发现BRCA1突变，2%的患者发现BRCA2突变。15%的患者（45例）发现了意义不明的变异。三阴性乳腺癌（TNBC）占所有BC和突变患者的86%。观察到以下三种常见的有害BRCA1创始人突变：在五名无亲缘关系的患者中观察到c.4136_4137delCT，在三名无亲缘关系的患者中观察到c.5530delC，在五名无亲缘关系的患者中观察到c.4524G>A突变。在BRCA1基因中鉴定出一种新突变（c.5512 dup [p.Glu1838Glyfs*42]）。结论 在高危沙特BC患者中，BRCA1突变很普遍（11%）。TNBC是最常见的BC亚型。此外，单独的年龄与突变没有显著关联，但年龄、家族史和TNBC等危险因素的组合与BRCA突变有显著关联。
