Mitochondrial DNA and Ovarian Cancer Risk and Survival
线粒体 DNA 与卵巢癌风险和生存
基本信息
- 批准号:8296141
- 负责人:
- 金额:$ 54.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-27 至 2017-04-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAlberta provinceBiologicalBiological MarkersBloodBody FluidsBritish ColumbiaCancer PatientCancerousCase-Control StudiesCellsCessation of lifeComplexCytotoxic ChemotherapyDNADNA copy numberDataDevelopmentDiagnosisDiagnostic Neoplasm StagingEarly DiagnosisEnsureEpigenetic ProcessEuropeanGenetic VariationGenomeGenotypeGoalsGrantHealthcare SystemsHigh-Risk CancerHistologyInterviewKnowledgeMalignant Female Reproductive System NeoplasmMalignant NeoplasmsMalignant neoplasm of ovaryMedicalMedical RecordsMitochondriaMitochondrial DNAMolecularMutationNuclearOvarianPathologistPathologyPlayPopulationPrimary PreventionRecruitment ActivityRecurrent diseaseRegimenResistanceResourcesRiskRisk FactorsRoleSalivaSamplingScreening for Ovarian CancerScreening procedureSingle-Payer SystemSiteSourceSpecimenTestingTherapeutic InterventionTimeTissue SampleTissuesTumor TissueVariantWomanWorkagedbasecancer riskcancer therapycarcinogenesiscase controlcostfollow-upimprovedindexingmodifiable riskmolecular markernext generationnovelnovel strategiesoutcome forecastovarian cancer preventionpopulation basedpreventtumor
项目摘要
DESCRIPTION (provided by applicant): Ovarian cancer is the most deadly gynecologic cancer. We are challenged on almost every front by this complex malignancy: few modifiable risk factor have been identified for primary prevention, current screening is neither sensitive nor
specific enough to use at the population level, and current cytotoxic therapy regimens (single or combined) extend survival but ultimately are ineffective as most ovarian cancer patients still die of chemo- resistant recurrent disease. A new understanding of key factors that contribute to cancer development and chemo-resistance is needed to inform the biological basis for novel interventions and therapies. An intriguing possibility is that mitochondria and mitochondrial DNA (mtDNA) play a role, as yet undefined, in ovarian cancer development and progression. Our overall goal is to understand how mtDNA can be used to predict women at elevated risk for ovarian cancer who may benefit from more intensive medical workups resulting in earlier diagnosis and to predict women who are most likely to benefit from specific therapies. Our working hypothesis is that women with ovarian cancer will have different polymorphic variants of mtDNA and/or a different distribution of mtDNA copy number in blood and cancerous tissue than similar women without ovarian cancer. We also hypothesize that one or more of these mtDNA features will be predictive of risk and survival. In testing our hypotheses, we will use extensive resources of the Ovarian Cancer in Alberta and British Columbia (OVAL-BC) Study, a population-based case-control study with ~1235 cases and 2070 controls recruited from 2002-2011. Existing data/specimens include extensive interview information and DNA from blood/buccal samples. We will augment this resource with detailed information on treatment and tumor histology as well as cancerous tissue samples. We have access to a leading next-generation sequencing platform for systematic and detailed characterization of mtDNA variation using index tags that act as molecular barcodes for simultaneous sequencing of up to 96 samples at a time, allowing us to completely sequence mtDNA from blood or saliva in very case and control and mtDNA from cancerous tissue in the cases. Our exceptional OVAL-BC Study resource, access to medical records and tissue, expert pathology review, and technological strength makes us uniquely poised to assess the effect of mitochondrial genetic variation on ovarian cancer risk and survival. Thus, by characterizing mtDNA and risk/survival in an existing and well- characterized population, we may, in the short-term, identify new biomarkers that could be further assessed in efforts to prevent death from ovarian cancer. Ultimately, such knowledge can be used to elicit more effective ovarian cancer prevention and treatment.
PUBLIC HEALTH RELEVANCE: Ovarian cancer is the most deadly gynecologic cancer. Our goal is to understand how mtDNA can be used to predict: 1) women who are at elevated risk for ovarian cancer who may benefit from more intensive medical workups resulting in earlier diagnosis; and, 2) women who are most likely to benefit from specific therapies. By characterizing mtDNA and risk and survival in an existing and well-characterized population, we may, in the short-term, identify new biomarkers that could be immediately relevant in efforts to prevent death from ovarian cancer. Ultimately, such knowledge can be used to elicit more effective ovarian cancer prevention and treatment.
描述(申请人提供):卵巢癌是最致命的妇科癌症。这种复杂的恶性肿瘤几乎在每个方面都对我们提出了挑战:很少有可改变的风险因素被确定为一级预防,目前的筛查既不敏感,
特异性足以在人群水平使用,目前的细胞毒性治疗方案(单一或联合)延长了生存期,但最终无效,因为大多数卵巢癌患者仍然死于化疗耐药的复发性疾病。需要对导致癌症发展和化疗耐药性的关键因素有新的认识,以告知新干预和治疗的生物学基础。一个有趣的可能性是,线粒体和线粒体DNA(mtDNA)在卵巢癌的发展和进展中发挥了作用,但尚未确定。我们的总体目标是了解mtDNA如何用于预测卵巢癌风险升高的女性,这些女性可能受益于更密集的医疗检查,从而更早地诊断,并预测最有可能受益于特定治疗的女性。我们的工作假设是,患有卵巢癌的女性与没有卵巢癌的相似女性相比,在血液和癌组织中具有不同的mtDNA多态性变体和/或mtDNA拷贝数的不同分布。我们还假设这些mtDNA特征中的一个或多个将预测风险和生存。在验证我们的假设时,我们将使用阿尔伯塔和不列颠哥伦比亚省卵巢癌研究(OVAL-BC)的广泛资源,这是一项基于人群的病例对照研究,从2002-2011年招募了约1235例病例和2070例对照。现有的数据/标本包括大量的访谈信息和血液/口腔样本的DNA。我们将增加这个资源与治疗和肿瘤组织学以及癌组织样本的详细信息。我们可以使用领先的下一代测序平台,使用索引标签作为分子条形码,一次同时对多达96个样本进行测序,从而对mtDNA变异进行系统和详细的表征,使我们能够对血液或唾液中的mtDNA进行完全测序,并对对照和癌组织中的mtDNA进行测序。我们卓越的OVAL-BC研究资源,医疗记录和组织的访问,专家病理学审查和技术实力使我们能够独特地评估线粒体遗传变异对卵巢癌风险和生存的影响。因此,通过在现有的和充分表征的人群中表征mtDNA和风险/生存,我们可以在短期内鉴定新的生物标志物,这些生物标志物可以在预防卵巢癌死亡的努力中进一步评估。最终,这些知识可用于更有效的卵巢癌预防和治疗。
公共卫生相关性:卵巢癌是最致命的妇科癌症。我们的目标是了解mtDNA如何用于预测:1)卵巢癌风险升高的女性,她们可能受益于更密集的医疗检查,从而更早诊断; 2)最有可能受益于特定治疗的女性。通过在现有的和充分表征的人群中表征mtDNA和风险以及生存率,我们可以在短期内确定新的生物标志物,这些生物标志物可能与预防卵巢癌死亡的努力直接相关。最终,这些知识可用于更有效的卵巢癌预防和治疗。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Linda S Cook其他文献
Databases and models : new tools for management
数据库和模型:新的管理工具
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
Eileen O Dareng;Simon G. Coetzee;J. Tyrer;Pei;Will L. Rosenow;Stephanie S. Chen;B. Davis;F. Dezem;Ji;Robbin Nameki;A. L. Reyes;Katja K.H. Aben;H. Anton;N. Antonenkova;G. Aravantinos;E. Bandera;L. B. Beane Freeman;M. W. Beckmann;A. Beeghly;Javier Benítez;Marcus Q Bernardini;L. Bjørge;A. Black;N. Bogdanova;Kelly L Bolton;J. D. Brenton;A. Budziłowska;R. Butzow;H. Cai;Ian Campbell;R. Cannioto;J. Chang;S. Chanock;Kexin Chen;G. Chenevix;Y. Chiew;Linda S Cook;Anna deFazio;J. Dennis;J. Doherty;T. Dörk;A. du Bois;M. Dürst;Diana M Eccles;G. Ene;Peter A. Fasching;James M. Flanagan;R. Fortner;F. Fostira;A. Gentry;Graham G. Giles;Marc T Goodman;J. Gronwald;C. Haiman;N. Håkansson;F. Heitz;Michelle A. Hildebrandt;E. Høgdall;C. K. Høgdall;R. Huang;A. Jensen;Michael E Jones;D. Kang;B. Karlan;A. Karnezis;Linda E. Kelemen;Catherine J. Kennedy;Elza K. Khusnutdinova;L. Kiemeney;S. K. Kjaer;J. Kupryjańczyk;Marilyne Labrie;D. Lambrechts;M. Larson;Nhu D Le;J. Lester;Lian Li;J. Lubiński;M. Lush;Jeffrey R Marks;K. Matsuo;T. May;John R. McLaughlin;I. McNeish;Usha Menon;Stacey Missmer;F. Modugno;M. Moffitt;Alvaro N Monteiro;K. Moysich;Steven A Narod;T. Nguyen;Kunle Odunsi;Håkan Olsson;N. Onland;Sue K Park;T. Pejovic;J. Permuth;A. Piskorz;D. Prokofyeva;Marjorie J. Riggan;Harvey A. Risch;C. Rodríguez‐Antona;M. Rossing;Dale P. Sandler;V. W. Setiawan;Kang Shan;Honglin Song;M. Southey;Helen Steed;R. Sutphen;Anthony J Swerdlow;Soo;K. Terry;P. Thompson;Liv Cecilie Vestrheim Thomsen;Linda Titus;B. Trabert;R. Travis;Shelley S. Tworoger;Elena Valen;E. Van Nieuwenhuysen;D. V. Edwards;R. Vierkant;P. Webb;Clarice R. Weinberg;Rayna Matsuno Weise;Nicolas Wentzensen;Emily White;S. Winham;Alicja Wolk;Y. Woo;Anna H Wu;Li Yan;D. Yannoukakos;Nur Zeinomar;W. Zheng;A. Ziogas;A. Berchuck;E. Goode;David G Huntsman;C. Pearce;S. Ramus;T. A. Sellers;M. Freedman;K. Lawrenson;J. Schildkraut;D. Hazelett;Jasmine T Plummer;Siddhartha P Kar;Michelle R. Jones;Paul D. P. Pharoah;S. Gayther - 通讯作者:
S. Gayther
Early menopause and hormone therapy as determinants for lung health outcomes: a secondary analysis using the PLCO trial.
早期绝经和激素治疗作为肺部健康结果的决定因素:使用 PLCO 试验的二次分析。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:10
- 作者:
Xiaochun Gai;Yue Feng;Tessa M Flores;Huining Kang;Hui Yu;Kimberly K Leslie;Yiliang Zhu;Jennifer A Doherty;Yan Guo;Steven A Belinsky;Linda S Cook;Shuguang Leng - 通讯作者:
Shuguang Leng
Linda S Cook的其他文献
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{{ truncateString('Linda S Cook', 18)}}的其他基金
A Population Based Study of Ketorolac and Ovarian Cancer Survival
酮咯酸与卵巢癌生存的人群研究
- 批准号:
10457136 - 财政年份:2020
- 资助金额:
$ 54.29万 - 项目类别:
A Population Based Study of Ketorolac and Ovarian Cancer Survival
酮咯酸与卵巢癌生存的人群研究
- 批准号:
9885784 - 财政年份:2020
- 资助金额:
$ 54.29万 - 项目类别:
A Population Based Study of Ketorolac and Ovarian Cancer Survival
酮咯酸与卵巢癌生存的人群研究
- 批准号:
10543498 - 财政年份:2020
- 资助金额:
$ 54.29万 - 项目类别:
Mitochondrial DNA and Ovarian Cancer Risk and Survival
线粒体 DNA 与卵巢癌风险和生存
- 批准号:
8660048 - 财政年份:2012
- 资助金额:
$ 54.29万 - 项目类别:
Mitochondrial DNA and Ovarian Cancer Risk and Survival
线粒体 DNA 与卵巢癌风险和生存
- 批准号:
9054818 - 财政年份:2012
- 资助金额:
$ 54.29万 - 项目类别:
Mitochondrial DNA and Ovarian Cancer Risk and Survival
线粒体 DNA 与卵巢癌风险和生存
- 批准号:
8517630 - 财政年份:2012
- 资助金额:
$ 54.29万 - 项目类别:
Uterine cancer survival disparities, Hispanic ethnicity, and comorbidities.
子宫癌生存差异、西班牙裔和合并症。
- 批准号:
7781057 - 财政年份:2009
- 资助金额:
$ 54.29万 - 项目类别:
Uterine cancer survival disparities, Hispanic ethnicity, and comorbidities.
子宫癌生存差异、西班牙裔和合并症。
- 批准号:
7941753 - 财政年份:2009
- 资助金额:
$ 54.29万 - 项目类别:
TAMOXIFEN THERAPY AND RISK OF COLORECTAL CANCER
他莫昔芬治疗与结直肠癌的风险
- 批准号:
2433759 - 财政年份:1997
- 资助金额:
$ 54.29万 - 项目类别:
TAMOXIFEN THERAPY AND RISK OF COLORECTAL CANCER
他莫昔芬治疗与结直肠癌的风险
- 批准号:
2748891 - 财政年份:1997
- 资助金额:
$ 54.29万 - 项目类别: