Resolving the cancer relevance of predisposition gene mutations
解决易感基因突变与癌症的相关性
基本信息
- 批准号:10454351
- 负责人:
- 金额:$ 93.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:ATM geneAddressAdjuvantAfrican AmericanAfrican American populationAgeAllelesAwardBARD1 geneBRCA1 MutationBRCA1 geneBRCA2 MutationBRCA2 geneBreast Cancer PatientBreast Cancer Risk FactorBreast Cancer therapyCDH1 geneCHEK2 geneClinicalCohort StudiesDataDecision MakingDiseaseEstrogen receptor negativeEstrogen receptor positiveExhibitsFamilyFamily history ofGene MutationGenesGeneticGenetic Predisposition to DiseaseGenetic studyGoalsGuidelinesHereditary Malignant NeoplasmHeritabilityIndividualInheritedMalignant NeoplasmsMammary NeoplasmsMedicalMedical GeneticsMetastatic breast cancerMinority GroupsModelingMutateNF1 geneNeoadjuvant TherapyPALB2 genePTEN genePathogenicityPatientsPenetrancePopulationRAD51C geneRiskRisk AssessmentRisk EstimateRisk ManagementSeriesSusceptibility GeneTP53 geneTest ResultVariantVisioncancer clinical trialcancer predispositioncancer riskclinical applicationclinically relevantgenetic panel testgenetic testinggenetic variantimprovedlifetime riskmalignant breast neoplasmmutation carriernovelrare variantrisk varianttargeted treatmenttherapy outcometranslational studytreatment responsetriple-negative invasive breast carcinomavariant of unknown significance
项目摘要
Breast cancer has a strong heritable component with approximately 15% of patients exhibiting a family history
of the disease. My group recently established that inherited variants in 12 genes (ATM, BARD1, BRCA1, BRCA2,
CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53) predispose to breast cancer (1, 2), that
variants in all 12 genes increase risks of breast cancer in minority populations (3), and that variants in certain
genes predispose only to estrogen receptor (ER) positive (ATM and CHEK2) or ER negative and triple negative
breast cancer (TNBC) (BARD1, RAD51C and RAD51D) (4-6). Despite these major advances, clinical application
of the information is still lacking. In addition, up to 50% of the familial risk of breast cancer remains unexplained.
Under this award we plan to address clinically relevant issues, including improved application of genetic testing
results for risk management of patients and improved selection of breast cancer therapy. In addition, we aim to
identify new breast cancer predisposition genes that account for the missing heritability. The proposed studies
are unified under a theme of advancing understanding of predisposition genetics. The studies are as follows:
A. Age-specific and population-specific cancer risk assessment for predisposition gene variants. Results from
hereditary multigene panel testing has limited clinical utility because only lifetime risk estimates of cancer by age
80 are available. Here we will estimate 5 and 10-year risks of breast cancer, so that patients can make decisions
about medical management. In addition, we have evidence that specific genes have much higher penetrance in
African Americans. We will determine the penetrance of predisposition gene variants using a large African
American cohort study in order to modify risk management guidelines for this population.
B. Functional characterization of predisposition gene variants. Variants of uncertain significance (VUS)
identified by genetic testing remain a major problem for individuals receiving clinical genetic testing. We aim to
combine high-throughput functional analysis of VUS in ATM, BRCA2 and PALB2 genes with genetic data from
families in integrated models to determine the clinical relevance of many VUS alterations.
C. Therapeutic response for breast cancer predisposition genes. The responsiveness of breast tumors
associated with predisposition gene variants to standard or targeted therapy is only known for BRCA1 and
BRCA2 mutation carriers. Here we aim to identify all patients with pathogenic variants in the commonly mutated
BRCA1, BRCA2, PALB2, ATM and CHEK2 genes from a series of neo-adjuvant, adjuvant and metastatic breast
cancer clinical trials and to assess response to therapy and outcome.
D. Identification of novel breast cancer predisposition alleles. The common and rare risk alleles for breast
cancer account for only 50% of the familial risk in the population. In an effort to identify the missing heritability
we will collaborate with Regeneron Inc. through our SIMPLEXO consortium to identify common and rare alleles
associated with breast cancer risk in 45,000 breast cancer patients.
乳腺癌具有很强的遗传成分,大约15%的患者有家族史
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Fergus Joseph Couch其他文献
Fergus Joseph Couch的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Fergus Joseph Couch', 18)}}的其他基金
BRCA1/2 and Hereditary Breast, Ovarian and Pancreatic (HBOP) Cancer Variant Curation Expert Panels
BRCA1/2 和遗传性乳腺癌、卵巢癌和胰腺癌 (HBOP) 癌症变异管理专家小组
- 批准号:
10412208 - 财政年份:2022
- 资助金额:
$ 93.35万 - 项目类别:
BRCA1/2 and Hereditary Breast, Ovarian and Pancreatic (HBOP) Cancer Variant Curation Expert Panels
BRCA1/2 和遗传性乳腺癌、卵巢癌和胰腺癌 (HBOP) 癌症变异管理专家小组
- 批准号:
10681272 - 财政年份:2022
- 资助金额:
$ 93.35万 - 项目类别:
Resolving the cancer relevance of predisposition gene mutations
解决易感基因突变与癌症的相关性
- 批准号:
10684726 - 财政年份:2020
- 资助金额:
$ 93.35万 - 项目类别:
Resolving the cancer relevance of predisposition gene mutations
解决易感基因突变与癌症的相关性
- 批准号:
10245286 - 财政年份:2020
- 资助金额:
$ 93.35万 - 项目类别:
Resolving the cancer relevance of predisposition gene mutations
解决易感基因突变与癌症的相关性
- 批准号:
10053431 - 财政年份:2020
- 资助金额:
$ 93.35万 - 项目类别:
The contribution of RAD51C and RAD51D to breast and ovarian cancer
RAD51C 和 RAD51D 对乳腺癌和卵巢癌的贡献
- 批准号:
10400738 - 财政年份:2018
- 资助金额:
$ 93.35万 - 项目类别:
The contribution of RAD51C and RAD51D to breast and ovarian cancer
RAD51C 和 RAD51D 对乳腺癌和卵巢癌的贡献
- 批准号:
10188458 - 财政年份:2018
- 资助金额:
$ 93.35万 - 项目类别:
Identifying and validating novel susceptibility genes for breast cancer
鉴定和验证乳腺癌的新易感基因
- 批准号:
8694379 - 财政年份:2014
- 资助金额:
$ 93.35万 - 项目类别:
Risk and penetrance of mutations from breast cancer testing panels.
乳腺癌检测组突变的风险和外显率。
- 批准号:
8827527 - 财政年份:2014
- 资助金额:
$ 93.35万 - 项目类别:
Risk and penetrance of mutations from breast cancer testing panels.
乳腺癌检测组突变的风险和外显率。
- 批准号:
9132729 - 财政年份:2014
- 资助金额:
$ 93.35万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 93.35万 - 项目类别:
Research Grant