印度人群遗传性乳腺癌和卵巢癌BRCA1/2基因突变谱分析

Q2 Medicine Asian Pacific Journal of Cancer Prevention Pub Date : 2024-12-01 DOI:10.31557/APJCP.2024.25.12.4145

Kunjal Lila, Harshita Bhanushali, MIlind Chanekar, Raj Jatale, Monisha Banerjee, Rakhi Bajpai Dixit, Aparna Rajadhyaksha, Kirti Chadha

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引用次数: 0

摘要

目的：本研究的目的是确定印度人群中与遗传性乳腺癌和卵巢癌（HBOC）相关的基因突变的患病率和谱，并评估BRCA突变类型、频率和发病率与年龄、性别、个人和家族史的相关性。方法：将2017年至2023年期间接受BRCA1/2检测的500名符合NCCN标准的印度HBOC患者纳入本研究。匿名数据是从医疗记录中检索的。在Thermo Ion GeneStudio™S5系统上使用Next Generation Sequencing （NGS）进行遗传分析，通过Sanger测序确认阳性突变。外周血样本按照ACMG指南进行DNA提取、文库制备和变异分类处理。结果：500例患者中，BRCA突变阳性119例（23.8%），阴性381例（76.2%）。BRCA发病机制、可能致病性和不确定意义变异（VUSs）的患病率分别为14.8%、1.6%和7.4%。在BRCA1/2阳性患者中共检测到128个突变。BRCA突变与患者和家族史之间存在统计学上显著的相关性。38.8%的突变患者有BC、OC或BC/OC家族史，7.6%有其他癌症。BRCA突变在46 ~ 65 y年龄组中占主导地位（26.2%）。在128个突变中，分别有59.3%（76/128）和40.6%（52/12）的患者存在BRCA1和BRCA2突变。错义突变在BRCA1（30.26%）和BRCA2（55.77%）基因中最为常见，其次是BRCA1和BRCA2中的移码突变（22.3%）和无义突变（17.3%）。结论：BRCA阳性检出率为23.8%。BRCA突变与患者和家族史之间存在统计学上显著的关联。

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Mutation Spectrum Analysis of BRCA1/2 Genes for Hereditary Breast and Ovarian Cancer in the Indian Population.

Objective: The objective of this study was to determine the prevalence and spectrum of genetic mutations linked to inherited breast and ovary cancer (HBOC) in the Indian population, and to evaluate the correlation of BRCA mutation types, frequency, and incidence with age, gender, and personal and family history.

Methods: A retrospective cohort of 500 Indian HBOC patients, meeting NCCN criteria who underwent BRCA1/2 testing from 2017 to 2023 were shortlisted for this study. The anonymized data was retrieved from medical records. Genetic analysis was conducted using Next Generation Sequencing (NGS) on the Thermo Ion GeneStudio™ S5 System, with positive mutations confirmed via Sanger sequencing. Peripheral blood samples were processed for DNA extraction, library preparation, and variant classification following ACMG guidelines.

Results: Out of the 500 patients, 119 (23.8%) were positive for BRCA mutations, and 381 (76.2%) were negative. The prevalence of BRCA pathogenesis, likely pathogenicity, and variants of uncertain significance (VUSs) were 14.8%, 1.6%, and 7.4%, respectively. A total of 128 mutations were detected in the positive BRCA1/2 patients. A statistically significant correlation was found between BRCA mutations with the patient and family history. A total of 38.8% of the patients with mutations had a family history of BC, OC or BC/OC, while 7.6% had other cancers. BRCA mutations were predominant (26.2%) in the age group of 46-65 Y. Among the 128 mutations, 59.3% (76/128) and 40.6% (52/12) of the patients had mutations in BRCA1 and BRCA2, respectively. Missense mutations were the most common in both the BRCA1 (30.26%) and BRCA2 (55.77%) genes, followed by frameshift (22.3%) and nonsense (17.3%) mutations in BRCA1 and BRCA2, respectively.

Conclusion: BRCA positivity was detected in 23.8% of the patients. A statistically significant association was shown between BRCA mutations and patient and family history.

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来源期刊

Asian Pacific Journal of Cancer Prevention 医学-肿瘤学

CiteScore

2.80

自引率

0.00%

发文量

779

审稿时长

3 months

期刊介绍： Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: -Epidemiology, detection and screening. -Cellular research and bio-markers. -Identification of bio-targets and agents with novel mechanisms of action. -Optimal clinical use of existing anti-cancer agents, including combination therapies. -Radiation and surgery. -Palliative care. -Patient adherence, quality of life, satisfaction. -Health economic evaluations.