Precision methylation biomarkers linked to cancer disparities

精确甲基化生物标志物与癌症差异相关

• 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
• 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

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.

项目摘要 任何女性都不应该死于宫颈癌，但宫颈癌是世界上女性第三大恶性肿瘤，仅次于 乳腺癌和结肠直肠癌。子宫颈癌也是其中最明显的差异存在的肿瘤之一 国际吧宫颈癌的发病率和死亡率在美国拉丁美洲人中已经高了几十年。 然而，最近发表的一项研究显示，美国白色和黑人妇女的宫颈癌死亡率要高得多。 在调整了直肠切除术的数量后，比以前认为的要高。黑人女性死于 宫颈癌的发病率比以前认为的高77%，白色妇女的死亡率高47%。悬殊 在排除子宫颈切除术后，按种族分列的宫颈癌死亡率翻了一番，从每10万名妇女中2.7人增加到5.4人。 死亡率计算。据推测，拉丁裔妇女的情况也是如此，但目前没有数据可以证实， 是这样的。 使用细胞学筛查（巴氏涂片）和致癌性人乳头瘤病毒（HPV+）基因分型是有效的， 识别可能有宫颈癌风险的女性，但不能用于预测谁更有可能患宫颈癌。 carcinoma.美国目前对持续HPV+感染和异常Pap的女性的实践标准是转诊至 阴道镜检查和随后的活检。然而，大多数这些活检（55%-70%）是在没有临床疾病的妇女中进行的 该项目的目标是证明CervicalMethDx Test商业化的可行性，这是一种精确的 宫颈癌筛查领域的甲基化。我们将重点关注持续致癌性人乳头瘤病毒患者 (HPV+）感染，谁是指阴道镜检查和随后的活检，即使大多数将有一个正常的活检。 我们正在与大卫Sidransky的研究实验室合作，以优化CervicalMethDx测试，并与教育和 约翰霍普金斯西德尼·金梅尔癌症中心外展部向居民介绍精确的表观遗传服务 巴尔的摩的低收入社区。HPV+妇女进入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，并减少美国现有的宫颈癌死亡率差距。