Precision methylation biomarkers linked to cancer disparities

精确甲基化生物标志物与癌症差异相关

基本信息

批准号：
9905229
负责人：
Rafael Guerrero-Preston
金额：
$ 20.6万
依托单位：
LIFEGENE-BIOMARKS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-24 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9905229
关键词：
Acetic Acids Africa African American Baltimore Biological Assay Biopsy Blinded Cancer Center Cancer Death Rates Caribbean region Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cervix carcinoma Clinical Colorectal Cancer Colposcopy Communities Country Cytology DNA DNA Sequence Data Developed Countries Developing Countries Disease Education and Outreach Emotional Epigenetic Process Evaluation Excision Genomics Genotype Glare Goals HPV-High Risk Health Health Care Costs Hour Human Human Papillomavirus Human papilloma virus infection Hysterectomy Incidence Innovation Corps Laboratory Research Latin American Latina Left Lesion Link Liquid substance Low income Malignant Neoplasms Malignant neoplasm of cervix uteri Methods Methylation Neighborhoods Oncogenic Pap smear Participant Patients Phase Pilot Projects Prospective Studies Protocols documentation Publishing Race Reflex action Retrospective Studies Risk Running Sampling Services Small Business Innovation Research Grant Specificity Squamous intraepithelial lesion Technology Testing Time Triage United States Vagina Validation Visual Woman Work arm base biomarker development bisulfite burden of illness cancer health disparity clinical risk commercialization cost follow-up health care quality improved instrument malignant breast neoplasm methylation biomarker mortality mortality disparity patient stratification prevent screening tumor validation studies

项目摘要

Project Summary No woman should die of cervical cancer, yet cervical cancer is the third leading malignancy among women in the world, after breast cancer and colorectal cancer. Cervical cancer is also one of the tumors in which the most glaring disparities exist worldwide. Cervical cancer incidence and mortality has been higher for decades among Latinas in the United States (US). However, a recently published study revealed that cervical cancer death rates among White and Black women in the US are much higher than previously thought, after adjusting for the number of hysterectomies performed. Black women are dying from cervical cancer at a rate 77% higher than previously thought, and white women are dying at a rate 47% higher. The disparity in cervical cancer mortality rates by race doubled, from 2.7 to 5.4 per 100,000 women, after removing women with hysterectomies from mortality calculations. Presumably, the same is the case for Latina women, but there is currently no data available to verify if this is the case. The use of cytology screening (Pap smear) and oncogenic Human papilloma Virus (HPV+) genotyping are effective in identifying women who may be at risk for cervical cancer, but cannot be used to predict who is more likely to develop cervical carcinoma. Current standard of practice in the US for women with persistent HPV+ infection and abnormal Pap is referral to colposcopy and subsequent biopsy. However, most of these biopsies (55%-70%) are performed in women without clinical disease The goal of this project is to demonstrate the feasibility for the commercialization of the CervicalMethDx Test, a precision methylation for the cervical cancer screening space. We will focus on patients with persistent oncogenic Human Papilloma Virus (HPV+) infection, who are referred into colposcopy and subsequent biopsy, even when most will have a normal biopsy. We are partnering with David Sidransky's research laboratory to optimize the CervicalMethDx Test and with the Education and Outreach Department of the Johns Hopkins Sidney Kimmel Cancer Center to introduce precision epigenetic services to residents of low-income neighborhoods in Baltimore. Efficient triage of HPV+ women into colposcopy will decrease unnecessary biopsies, improve health care quality, decrease health care costs, and reduce existing cervical cancer mortality disparities in the US.

项目概要任何女性都不应该死于宫颈癌，但宫颈癌是世界上第三大女性恶性肿瘤，仅次于宫颈癌。乳腺癌和结直肠癌。宫颈癌也是差异最明显的肿瘤之一全世界。几十年来，美国拉丁裔的宫颈癌发病率和死亡率一直较高。然而，最近发表的一项研究显示，美国白人和黑人女性的宫颈癌死亡率要高得多。在调整了子宫切除术的数量后，这一数字高于之前的预期。黑人妇女正在死于宫颈癌的发病率比之前认为的高 77%，白人女性的死亡率高出 47%。差异在于在切除子宫切除术后，按种族划分的宫颈癌死亡率翻了一番，从每 10 万名女性 2.7 人增至 5.4 人从死亡率计算。据推测，拉丁裔女性的情况也是如此，但目前没有数据可以证实是否情况就是如此。使用细胞学筛查（巴氏涂片）和致癌人乳头瘤病毒 (HPV+) 基因分型可有效识别可能有患宫颈癌风险的女性，但不能用于预测谁更有可能患宫颈癌癌。美国目前针对持续 HPV+ 感染且巴氏涂片异常的女性的实践标准可参考阴道镜检查和随后的活检。然而，大多数活检 (55%-70%) 是在没有临床疾病的女性中进行的该项目的目标是展示 CervicalMethDx 测试商业化的可行性，这是一种精密的测试宫颈癌筛查空间的甲基化。我们将重点关注患有持续致癌人乳头瘤病毒的患者 (HPV+) 感染，即使大多数人的活检结果正常，也会被转介接受阴道镜检查和随后的活检。我们正在与 David Sidransky 的研究实验室合作，优化 CervicalMethDx 测试，并与教育和约翰·霍普金斯大学西德尼·金梅尔癌症中心外展部向居民介绍精准表观遗传学服务巴尔的摩的低收入社区。对 HPV+ 女性进行阴道镜检查的有效分类将减少不必要的活检，提高医疗保健质量，降低医疗保健成本，并缩小美国现有的宫颈癌死亡率差异。