Establishing West African Oncogenetics Network

项目摘要 本申请是为回应特别利益通知(NOSI)而提出的，该通知被确认为非- CA-20-032。乳腺癌是非洲最常见的女性恶性肿瘤，是全球关注的健康问题。它的 在过去20年中，非洲的发病率和死亡率有所上升。高级演示文稿延迟 疾病和低存活率是撒哈拉以南非洲(SSA)妇女乳腺癌的特征，但在那里 没有筛查计划。可以使用遗传和非遗传风险因素来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能具有成本效益。使用《尼日利亚人报》的数据 乳腺癌研究(NBCS)，我们开发了一种适用于非洲的乳腺癌风险评估模型 妇女具有极好的识别准确率，但其实用性尚未在实践中得到评估。此外， 癌症遗传学的进步可以确定遗传性乳腺癌的高风险或非常高风险的女性。最近， 我们发现，在尼日利亚、喀麦隆和乌干达，连续患有乳腺癌的女性中约有15%携带 BRCA1/2等易感基因的突变。然而，SSA中的女性有遗传乳房和 卵巢癌无法获得挽救生命的遗传咨询和可操作的基因组测试。我们已经推出了 一项初步的遗传咨询和检测研究，招募了362名未经选择的乳房、卵巢、 子宫内膜癌和前列腺癌以及10名转介的一级亲属(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加强和加强正在进行的工作 在尼日利亚开展癌症基因组学研究培训，并测试将这项服务扩展到喀麦隆的可行性 以及尼日利亚的其他医院。我们建议再招收200名乳腺癌患者和他们的第一学位 亲属解决三个具体目标。首先，我们的目标是评估NBCS风险的可行性和实用性 评估工具，并评估西方乳腺癌患者女性亲属患乳腺癌的风险 非洲使用风险工具。第二，确定乳腺癌患者及其亲属的意愿 接受遗传性癌症的遗传咨询和检测，并支付费用。第三，我们接下来将进行 世代测序、基因测试和评估种族特有的多基因风险评分。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。 我们的长期目标是形成泛非肿瘤遗传学网络，从西非开始，通过建立 以家庭为基础的高危妇女基因筛查，使这些妇女有机会得到预防 或者在乳腺癌最有可能治愈的时候及早发现。这笔补充赠款将具有重要意义。 强化这一使命。

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.