Enhancing Global Diversity in Cancer Clinical Genetics

项目摘要/摘要 本申请是为了回应被确认为非CA-CA的特殊利益通知(NOSI)而提交的 20-032. 遗传遗传信息可以使用患者的方案来降低癌症风险和死亡率 确定、检测、咨询、预防和治疗。越来越多的证据表明，遗传基因 突变在撒哈拉以南非洲(SSA)的癌症病例中占很大比例。尼日利亚的乳腺癌 病例的遗传易感性突变率是美国白人的2.5倍，其中BRCA2是 尼日利亚乳腺癌中最常见的突变，与之相比，BRCA和TP53突变的比率更高 对卢旺达高加索人的观察。这些初步意见突出表明，有必要进一步 更好地定义SSA中乳腺癌风险遗传的大型研究。 大多数癌症基因测试数据并不代表美国或全球的种族和民族多样性 人口。癌症遗传学研究中不同人群的这种不足限制了这些数据在 所有人口。此外，已经证明，当基因多样化时，可能会出现遗传误诊。 在作出关于致病性和风险的推断时，不包括种群及其突变谱 并可能加剧健康差距。因此，包括更广泛的癌症个体的研究 遗传学研究将造福于所有人群。 为了开发和评估SSA中基因检测的潜力，我们提出了一个概念证明 遗传性癌症的可行性研究将有助于提供遗传性癌症突变患病率的数据 在SSA，并为制定针对SSA的癌症基因检测指南提供信息。我们将解决 通过承担以下具体目标实现这些目标：具体目标1：制定和评估一套 用于癌症基因检测、咨询和低资源管理的基本癌症遗传方案 环境；和具体目标2：在#年对研究、基因检测和咨询进行试点评估 卢旺达的乳腺癌和前列腺癌病例。 拟议的先导研究不仅将加强SSA的癌症遗传学研究和临床翻译 但将解决在癌症遗传学数据中增加种族多样性的迫切需要，到目前为止 主要由欧洲血统数据主导。不同种族的基因数据将有助于适当的发展 并在所有人群中实施癌症基因测试，特别是将减少 美国人群中的遗传误诊和对癌症遗传风险的改进解释。

PROJECT SUMMARY/ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 20-032. Inherited genetic information can reduce cancer risk and mortality using protocols for patient ascertainment, testing, counseling, prevention, and treatment. There is growing evidence that inherited genetic mutations represent a large proportion of cancer cases in sub-Saharan Africa (SSA). Nigerian breast cancer cases have a 2.5-fold higher rate of inherited susceptibility mutations than US Whites, with BRCA2 being the most commonly mutated in Nigerian breast cancer, and higher rates of BRCA and TP53 mutations compared to observations made in Caucasians in Rwanda. These preliminary observations highlight the need for further large studies to better define the inheritance of breast cancer risk in SSA. Most cancer genetic testing data does not represent the racial and ethnic diversity of the US or global population. This deficit of diverse populations in cancer genetics research limits the application of these data to all populations. In addition, it has been demonstrated that genetic misdiagnoses can arise when diverse populations and their mutational spectrum is not included when making inferences about pathogenicity and risk and can exacerbate health disparities. Thus, studies that include a broader spectrum of individuals in cancer genetics research will benefit all populations. In order to develop and evaluate the potential for genetic testing in SSA, we propose a proof of concept feasibility study of hereditary cancer that will contribute data on the prevalence of hereditary cancer mutations in SSA and inform the development of SSA-specific guidelines for cancer genetic testing. We will address these goals by undertaking the following specific aims: Specific Aim 1: Develop and evaluate a set of essential cancer genetic protocols for cancer genetic testing, counseling, and management in low resource settings; and Specific Aim 2: Undertake a pilot evaluation of research genetic testing and counseling in 100 breast and prostate cancer cases in Rwanda. The proposed pilot research will not only enhance cancer genetics research and clinical translation in SSA but will address the critical need for increased ethnic diversity in cancer genetics data, which to date has been dominated by European ancestry data. Ethnically diverse genetic data will aid in the appropriate development and implementation of cancer genetic testing for all populations, and in particular will reduce the potential for genetic misdiagnoses and improved interpretation of cancer genetic risk in US populations.