CAMPO Global Cancer Health Disparities Supplement

CAMPO 全球癌症健康差异补充资料

基本信息

批准号：
10166395
负责人：
ANA Patricia ORTIZ
金额：
$ 19.49万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2019-09-12 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166395
关键词：
Address Algorithms Anus Biopsy Butyrates California Cervical Cities Classification Clinic Clinical Data Cytology Data Detection Development Diagnosis Diagnostic tests Diet Dietary intake Disease Education Enrollment Food Frequencies Future Genes Genetic Genomic DNA Goals HIV HIV Seropositivity Hispanics Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Incidence Inflammatory Infrastructure Latin America Life Style Light Location Malignant Neoplasms Malignant neoplasm of anus Measurement Mediating Methylation Mexican Mexico Neoplasms Oncoproteins Outcome Parents Participant Phase Population Prevention Probiotics Puerto Rico Questionnaires Regimen Research Resolution Risk Role San Francisco Site Specimen Squamous intraepithelial lesion Swab Testing Time Woman biobank cancer health disparity cancer risk cervical and anal cancer clinical care design high risk high risk population interest men men who have sex with men microbiome microbiome analysis microbiota microbiota profiles novel therapeutics parent grant random forest recruit response screening sex sociodemographics therapeutic vaccine

项目摘要

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-032. This is a supplement to U54 CA242646, “California-Mexico-Puerto Rico Partnership (CAMPO) Center for Prevention of HPV-related Cancer in HIV+ Populations”. The parent grant's focus is to perform research on reducing the risk of cervical and anal cancer in men and women living with HIV in Latin America. CAMPO Study 1 will enroll 4000 women and 1000 men living with HIV to optimize screening algorithms to detect cervical and anal high-grade squamous intraepithelial lesions (HSIL). The incidence of anal cancer is high among all groups of Hispanic people living with HIV (PLWH), especially among those in Puerto Rico (PR). HPV infection is necessary but insufficient for the development of anal HSIL and cancer. The goal of this supplement is to elucidate the role of the anal microbiome as a contributor to this increased risk of anal cancer risk in these high-risk populations. Specific aims are 1) Study the relationship between anal high- risk HPV (hr-HPV) infection and the anal microbiome among three distinct populations of Hispanic PLWH in California, Mexico and PR; and 2) Study the relationship between anal HSIL and the anal microbiome among three distinct populations of Hispanic PLWH with anal hr-HPV infection. These populations are of particular interest given their divergent lifestyles but similarity in genetic background. We hypothesize that among Hispanic PLWH without anal HSIL, the microbiome will be different among those with and without hr-HPV infection. We hypothesize that the proportion with pro-inflammatory-mediating taxa will be highest among the PR population compared with the Mexican and California populations given the higher incidence in anal cancer in PR. We also hypothesize that among Hispanic PLWH with anal hr-HPV at the 3 locations, detection of HSIL will be associated with a pro-inflammatory microbiome and a decrease in butyrate-producing signatures, with the proportion with pro-inflammatory changes highest in PR compared with the other populations. We will enroll 100 PLWH (50 men and 50 women) at each of the PR, Mexico City and San Francisco CAMPO sites, for a total of 300 Hispanic PLWH. Data on anal HPV, anal cytology and anal HSIL will be available through CAMPO Study 1 in PR and Mexico City, and from the San Francisco ANCRE Clinic, where PLWH are screened for anal HSIL as part of routine clinical care. A validated food frequency questionnaire in Spanish will be administered to assess dietary intake for the previous 3 and 6 months. Anal swab specimens will be retrieved from the CAMPO Biorepository and used for microbiome analysis. The 16S gene will be amplified from extracted anal swab genomic DNA and subjected to Illumina Miseq. Sequences of the 16S gene V4 region will be analyzed in QIIME2. Random forest classification will be performed to understand how our predictors, i.e. microbiome variables (diversity measurements, species-level taxa) and other covariates (sociodemographics, sex, diet, clinical data, etc.), are associated with hr-HPV infection or HSIL (outcomes).

抽象的本申请是为了响应特殊利益通知（NOSI）而提交的，该通知被确定为 NOT-CA-20-032。这是 U54 CA242646“加利福尼亚-墨西哥-波多黎各伙伴关系”的补充。 (CAMPO) HIV+ 人群中 HPV 相关癌症预防中心”。开展降低拉丁语艾滋病毒感染者患宫颈癌和肛门癌风险的研究美国 CAMPO 研究 1 将招募 4000 名感染艾滋病毒的女性和 1000 名男性，以优化筛查检测宫颈和肛门高级鳞状上皮内病变（HSIL）的算法。在所有西班牙裔艾滋病毒感染者 (PLWH) 群体中，肛门癌的发病率很高，尤其是在波多黎各 (PR)。HPV 感染对于肛门 HSIL 和癌症的发展是必要的，但还不够。该补充剂的目标是阐明肛门微生物组在导致肛门直肠癌风险增加的因素中所扮演的角色这些高危人群的肛门癌风险具体目标是 1) 研究肛门高危人群之间的关系。西班牙裔 PLWH 三个不同人群中的危险 HPV (hr-HPV) 感染和肛门微生物组加利福尼亚州、墨西哥和波多黎各；2) 研究肛门 HSIL 与肛门微生物组之间的关系肛门 hr-HPV 感染的西班牙裔 PLWH 的三个不同人群这些人群具有特殊性。鉴于他们的生活方式不同但遗传背景相似，他们对这一点很感兴趣。没有肛门 HSIL 的西班牙裔 PLWH，感染和不感染 hr-HPV 的微生物组会有所不同我们认为促炎症介导类群的比例在所有感染中最高。鉴于肛门癌的发病率较高，PR 人群与墨西哥和加利福尼亚人群相比在公关方面，我们还加强了在 3 个地点感染肛门 hr-HPV 的西班牙裔感染者中 HSIL 的检测。将与促炎微生物组和丁酸盐产生特征的减少有关，与其他人群相比，PR 人群中促炎症变化的比例最高。我们将在 PR、墨西哥城和旧金山各招募 100 名 PLWH（50 名男性和 50 名女性） CAMPO 网站将收集总共 300 名西班牙裔 PLWH 的肛门 HPV、肛门细胞学和肛门 HSIL 数据。可通过 PR 和墨西哥城的 CAMPO 研究 1 以及旧金山 ANCRE 诊所获得，其中作为常规临床护理的一部分，对 PLWH 进行肛门 HSIL 筛查。将使用西班牙语来评估过去 3 个月和 6 个月的肛门拭子样本的饮食摄入量。将从 CAMPO 生物储存库检索并用于微生物组分析。 16S 基因将被检索。从提取的肛门拭子基因组 DNA 中扩增并进行 16S 基因的 Illumina Miseq 序列分析。将在 QIIME2 中分析 V4 区域，以了解我们的随机森林分类是如何进行的。预测变量，即微生物组变量（多样性测量、物种级分类群）和其他协变量（社会人口统计学、性别、饮食、临床数据等）与 hr-HPV 感染或 HSIL（结果）相关。