Pharmacogenetics of Tamoxifen and Chemotherapies and Risk of Contralateral Breast

他莫昔芬和化疗的药物遗传学以及对侧乳房的风险

基本信息

  • 批准号:
    7663549
  • 负责人:
  • 金额:
    $ 8.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-06-01 至 2011-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Adjuvant chemotherapy and tamoxifen have been shown to reduce the risk of contralateral breast cancer (CBC) among women with a previous history of breast cancer. It is well recognized that not all individuals metabolize drugs with the same efficiency or experience the same likelihood of adverse side effects related to treatment. Additional information predicting metabolic capacity and outcomes may optimize an individual's response to drug therapy and improve clinical outcomes. Common genetic polymorphisms in drug metabolizing enzymes, functional targets and drug transporters may be key in this distinction. In this pharmacogenetic study, we intend to genotype a key set of functional polymorphisms in metabolic genes in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study, a large, population-based, case-control study of women with unilateral and bilateral breast cancer that has systematically collected treatment and outcome data. We will investigate whether selected functional variants in genes involved in the metabolism of tamoxifen and other chemotherapeutic agents modify the protective effect of these treatments on the risk of CBC in the WECARE Study. We consider functional polymorphisms in the following key genes involved in the metabolism of tamoxifen (i.e., CYP2D6, CYP3A5, SULT1A1, UGT2B15) and drugs commonly used in polychemotherapy regimens for breast cancer including: cyclophosphamide (i.e., CYP3A5, GSTM1, GSTP1, GSTT1); anthracyclines (i.e., CYP3A5, MDR1, GSTM1, GSTP1, GSTT1) and antimetabolites (i.e., DHFR, TS, MTHFR) .We propose to genotype 634 women with bilateral breast cancer and 1,158 unilateral breast cancer controls who received the chemotherapy or tamoxifen as treatment for first primary breast cancer. We propose a study design that maximizes available information regarding genetic variability in these key pathways by examining candidate polymorphisms with known or likely functional effects. We plan several follow-up projects using data from this study including incorporating the genotype data collected on the functional polymorphisms in this study with tagSNPs on the Illumina 650K and additional data collection on 1,600 women from a genome-wide study that is expected to be funded in WECARE Study. This will allow for pooled analyses to pursue subgroup analyses and pathway-based statistical modeling approaches. This study uses an efficient approach to address research questions regarding the pharmacogenetics of commonly used therapies and risk of CBC among women younger than 55 years, which has not previously been addressed. These results will contribute to our knowledge base and help improve upon current clinical strategies to determine the right drug for individualized care that minimizes adverse events and maximizes long-term outcomes.
描述(由申请人提供):辅助化疗和他莫昔芬已被证明可以降低既往有乳腺癌病史的女性患对侧乳腺癌(CBC)的风险。众所周知,并非所有个体都以相同的效率代谢药物或经历与治疗相关的不良副作用的可能性相同。预测代谢能力和结果的额外信息可以优化个体对药物治疗的反应并改善临床结果。药物代谢酶、功能靶点和药物转运蛋白的常见遗传多态性可能是这种区别的关键。在这项药物遗传学研究中,我们打算对妇女环境、癌症和放射流行病学(WECARE)研究中代谢基因的一组关键功能多态性进行基因分型,WECARE研究是一项针对单侧和双侧乳腺癌妇女的大型、基于人群的病例对照研究,系统收集了治疗和结局数据。我们将研究在WECARE研究中,他莫昔芬和其他化疗药物代谢相关基因的选定功能变体是否会改变这些治疗对CBC风险的保护作用。我们考虑了以下参与他莫昔芬代谢的关键基因的功能多态性(即,CYP2D6、CYP3A5、SULT 1A1、UGT 2B15)和乳腺癌综合化疗方案中常用的药物,包括:环磷酰胺(即,CYP3A5、GSTM1、GSTP1、GSTT1);蒽环类(即,CYP3A5、MDR 1、GSTM 1、GSTP 1、GSTT1)和抗代谢物(即,我们建议对634名双侧乳腺癌妇女和1,158名单侧乳腺癌对照妇女进行基因分型,这些妇女接受化疗或他莫昔芬作为首次原发性乳腺癌的治疗。我们提出了一个研究设计,最大限度地利用现有的信息,通过检查候选多态性与已知的或可能的功能性影响,在这些关键途径的遗传变异。我们计划使用本研究的数据进行几个后续项目,包括将本研究中收集的功能多态性的基因型数据与Illumina 650K上的tagSNP结合起来,以及从全基因组研究中收集的1,600名女性的额外数据,该研究预计将在WECARE研究中获得资助。这将允许汇总分析进行亚组分析和基于路径的统计建模方法。这项研究使用了一种有效的方法来解决有关常用疗法的药物遗传学和年龄小于55岁的女性CBC风险的研究问题,这是以前没有解决的问题。这些结果将有助于我们的知识基础,并有助于改善目前的临床策略,以确定合适的药物进行个性化护理,最大限度地减少不良事件和最大限度地提高长期结果。

项目成果

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Jane C. Figueiredo其他文献

Genetic variation in insulin pathway genes and distal colorectal adenoma risk
胰岛素途径基因的遗传变异与远端结直肠腺瘤风险
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    2.8
  • 作者:
    A. Levine;U. Ihenacho;Won H. Lee;Jane C. Figueiredo;David J. VanDenBerg;C. Edlund;Brian D Davis;Mariana C. Stern;Robert W. Haile
  • 通讯作者:
    Robert W. Haile
de novo metastases in patients with primary colorectal cancer: a Surveillance, Epidemiology, and End Results analysis
  • DOI:
    10.1007/s10552-025-02002-6
  • 发表时间:
    2025-04-19
  • 期刊:
  • 影响因子:
    2.100
  • 作者:
    Nicole C. Loroña;Kamya Sankar;Mariana C. Stern;Stephanie L. Schmit;Jane C. Figueiredo
  • 通讯作者:
    Jane C. Figueiredo
Sa1080: AN EVALUATION OF THE ASSOCIATION BETWEEN INFLAMMATION-ASSOCIATED BIOMARKERS AND MICROSATELLITE INSTABLILITY IN COLORECTAL CANCER
  • DOI:
    10.1016/s0016-5085(22)60707-8
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Holli A. Loomans-Kropp;Asad Umar;Jennifer Ose;Tengda Lin;Caroline Himbert;Christy A. Warby;Anjelica Ashworth;Sheetal Hardikar;Jurgen Bohm;Biljana Gigic;Petra Schrotz-King;Lin Zielske;Martin Schneider;Alexis B. Ulrich;David Shibata;Jane C. Figueiredo;Erin Siegel;Christopher I. Li;Adetunji Toriola;Cornelia Ulrich
  • 通讯作者:
    Cornelia Ulrich
Multi-tissue expression and splicing data prioritise anatomical subsite- and sex-specific colorectal cancer susceptibility genes
多组织表达和剪接数据优先考虑解剖亚位点和性别特异性结直肠癌易感基因
  • DOI:
    10.1038/s41467-025-60275-6
  • 发表时间:
    2025-05-30
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Emma Hazelwood;Daffodil M. Canson;Benedita Deslandes;Xuemin Wang;Pik Fang Kho;Danny Legge;Andrei-Emil Constantinescu;Matthew A. Lee;D. Timothy Bishop;Andrew T. Chan;Stephen B. Gruber;Jochen Hampe;Loic Le Marchand;Michael O. Woods;Rish K. Pai;Stephanie L. Schmit;Jane C. Figueiredo;Wei Zheng;Jeroen R. Huyghe;Neil Murphy;Marc J. Gunter;Tom G. Richardson;Vicki L. J. Whitehall;Emma E. Vincent;Dylan M. Glubb;Tracy A. O’Mara
  • 通讯作者:
    Tracy A. O’Mara
Examining Explicit Stereotype Perceptions of Colorectal Cancer Screening and Diagnosis in the Hispanic Community
  • DOI:
    10.1007/s13187-025-02609-y
  • 发表时间:
    2025-03-26
  • 期刊:
  • 影响因子:
    1.300
  • 作者:
    Aidan Foley;Bianca Luna-Lupercio;Jessica M. Capaldi;Galen Wiens-Cook;Vinicius Calsavara;Zulfikarali Surani;Sarah-Jeanne Salvy;Jane C. Figueiredo;Robert Haile;Nenette A. Cáceres;Celina H. Shirazipour
  • 通讯作者:
    Celina H. Shirazipour

Jane C. Figueiredo的其他文献

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{{ truncateString('Jane C. Figueiredo', 18)}}的其他基金

Admin-Core-001
管理核心-001
  • 批准号:
    10709124
  • 财政年份:
    2022
  • 资助金额:
    $ 8.15万
  • 项目类别:
Admin-Core-001
管理核心-001
  • 批准号:
    10709118
  • 财政年份:
    2022
  • 资助金额:
    $ 8.15万
  • 项目类别:
Biological determinants of colorectal cancer outcomes in Latinos of diverseýancestral origins
不同祖先起源的拉丁裔结直肠癌结果的生物决定因素
  • 批准号:
    10612712
  • 财政年份:
    2021
  • 资助金额:
    $ 8.15万
  • 项目类别:
Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
限时饮食与癌症:临床结果、机制和调节因素
  • 批准号:
    10179205
  • 财政年份:
    2021
  • 资助金额:
    $ 8.15万
  • 项目类别:
Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
限时饮食与癌症:临床结果、机制和调节因素
  • 批准号:
    10643869
  • 财政年份:
    2021
  • 资助金额:
    $ 8.15万
  • 项目类别:
Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
限时饮食与癌症:临床结果、机制和调节因素
  • 批准号:
    10428508
  • 财政年份:
    2021
  • 资助金额:
    $ 8.15万
  • 项目类别:
Biological determinants of colorectal cancer outcomes in Latinos of diverseýancestral origins
不同祖先起源的拉丁裔结直肠癌结果的生物决定因素
  • 批准号:
    10321976
  • 财政年份:
    2021
  • 资助金额:
    $ 8.15万
  • 项目类别:
Novel Biomarkers for Cancer-Related Fatigue: Integrating Metabolomics, Genomics and Behaviors
癌症相关疲劳的新型生物标志物:整合代谢组学、基因组学和行为
  • 批准号:
    9973799
  • 财政年份:
    2020
  • 资助金额:
    $ 8.15万
  • 项目类别:
Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2
SARS-CoV-2 免疫炎症反应的多样性和决定因素
  • 批准号:
    10855003
  • 财政年份:
    2020
  • 资助金额:
    $ 8.15万
  • 项目类别:
CORALE-SeroNet Recruitment and Biobanking Core
CORALE-SeroNet 招聘和生物样本库核心
  • 批准号:
    10222434
  • 财政年份:
    2020
  • 资助金额:
    $ 8.15万
  • 项目类别:

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