Establishing West African Oncogenetics Network

项目摘要 本申请是为了回应特别利益通知（NOSI）而提交的，该通知被确定为不- CA-20-032乳腺癌是非洲最常见的女性恶性肿瘤，是一个全球性的健康问题。其 非洲的发病率和死亡率在过去二十年中有所上升。晚期出现 疾病和生存率低是撒哈拉以南非洲（SSA）妇女乳腺癌的标志，但在那里， 没有筛选程序。遗传和非遗传风险因素可用于识别风险增加的妇女 因此，在资源有限的情况下，基于风险的筛查策略可以具有成本效益。根据尼日利亚的数据， 乳腺癌研究（NBCS），我们开发了一个适合非洲人的乳腺癌风险评估模型， 女性具有良好的辨别准确性，但其实用性尚未在实践中进行评估。此外，委员会认为， 癌症遗传学的进步可以识别出遗传性乳腺癌高风险或极高风险的妇女。最近， 我们发现，在尼日利亚、喀麦隆和乌干达，大约15%的连续患乳腺癌的妇女携带 易感基因突变，如BRCA 1/2。然而，撒哈拉以南非洲有遗传性乳腺癌风险的妇女， 卵巢癌患者无法获得挽救生命的遗传咨询和可行的基因组检测。我们推出 一项初步的遗传咨询和检测研究，招募了362名患有乳腺癌，卵巢癌， 子宫内膜癌和前列腺癌以及10名一级亲属（FDR）通过我们的合作者在 伊巴丹大学拟议的补充项目将有助于提高和加强正在进行的 在尼日利亚进行癌症基因组学的研究培训，并测试将服务扩展到喀麦隆的可行性 和其他尼日利亚的医院。我们建议增加200名乳腺癌患者及其第一学位 亲属要达到三个具体目标。首先，我们的目标是评估NBCS风险的可行性和效用 评估工具，并估计西方乳腺癌患者女性亲属中的乳腺癌风险 非洲使用风险工具。第二，我们将确定乳腺癌患者及其亲属的意愿 接受并支付遗传咨询和遗传癌症检测的费用。第三，我们接下来要进行 代测序基因检测和评估种族特异性多基因风险评分。我们将与 喀麦隆的研究人员将我们的遗传咨询工具和NBCS风险评估工具翻译成法语。 我们的长期目标是建立一个泛非肿瘤遗传学网络，从西非开始， 以家庭为基础的高风险妇女的遗传筛查，使这些妇女将有机会预防 或在乳腺癌最有可能治愈的时候及早发现。补充补助金将意义重大 加强这个使命。

PROJECT ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT- CA-20-032. Breast cancer is a global health concern as the most common female malignancy in Africa. Its incidence and mortality rates in Africa have increased in the last two decades. Late presentation with advanced disease and poor survival are the hallmarks of breast cancer in women in sub-Sahara Africa (SSA), but there is no screening program. Genetic and non-genetic risk factors can be used to identify women at increased risk so risk-based screening strategies can be cost effective in resource-limited setting. Using data from the Nigerian Breast Cancer Study (NBCS), we have developed a breast cancer risk assessment model suitable for African women with excellent discriminating accuracy but its utility has yet to be evaluated in practice. Furthermore, advances in cancer genetics can identify women at high or very high risk for inherited breast cancer. Recently, we found about 15% of consecutive women with breast cancer in Nigeria, Cameroon, and Uganda carried mutations in susceptibility genes such as BRCA1/2. However, women in SSA at risk for inherited breast and ovarian cancers lack access to lifesaving genetic counseling and actionable genomic tests. We have launched a preliminary genetic counseling and testing study, and enrolled 362 unselected patients with breast, ovarian, endometrial and prostate cancers and 10 referred first degree relatives (FDRs) in through our Collaborators at the University of Ibadan. The proposed supplemental project will help to enhance and strengthen ongoing research training in cancer genomics in Nigeria and test the feasibility of extending the service to Cameroon and other hospitals in Nigeria. We propose to enroll additional 200 breast cancer patients and their first degree relatives to address three specific aims. First, we aim to evaluate the feasibility and utility of NBCS risk assessment tool, and estimate breast cancer risk among female relatives of breast cancer patients in West Africa using the risk tool. Second, we will determine the willingness of breast cancer patients and their relatives to undergo and pay for genetic counseling and testing for inherited cancer. Third, we will conduct next generation sequencing genetic testing and assess ethnic specific Polygenic Risk Score. We will work with investigators in Cameroon to translate our Genetic Counseling tools and NBCS risk assessment tool to French. Our long-term goal is to form a Pan-African Oncogenetics Network, starting in West Africa, by establishing family based genetic screening of high risk women so that these women will have the opportunity for prevention or early detection of breast cancer when it is potentially most curable. The supplemental grant will significant enhance this mission.