The Impact of Gut Microbiota on the Sex Difference in Bladder Cancer

肠道菌群对膀胱癌性别差异的影响

基本信息

批准号：
10323683
负责人：
Xue Sean Li
金额：
$ 19.13万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-04 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323683
关键词：
Address Age Androgen Metabolism Androgens Antibiotics Biological Biology Bladder Bladder Neoplasm Cancer Biology Cancer Patient Cells Coupled Critiques Epigenetic Process Estrogens Feedback Female Four Core Genotypes Funding Opportunities Genitourinary system Genomic approach Geography Goals Gonadal Steroid Hormones Grant Health Care Costs Hormone use House mice Human body Incidence Individual Knowledge Light Male Castration Malignant Neoplasms Malignant neoplasm of urinary bladder Medical Microbe Mus Nature Outcome Phenotype Play Recurrence Reporting Research Role Sex Bias Sex Chromosomes Sex Differences Shapes Testing Testosterone Time Variant Woman X Chromosome cancer health disparity cancer initiation cancer risk cancer therapy cancer type checkpoint inhibition chemical carcinogen commensal microbes design fecal transplantation gender disparity genetic approach germ free condition gut microbes gut microbiota improved innovation insight male men microbial microbial community microbiome microbiota microorganism mortality response sex sex disparity socioeconomics trend tumor tumor growth

项目摘要

Men are 3-5 times more likely than women to develop and die from bladder cancer (BCa) but the underlying mechanisms of these gender disparities in BCa are poorly understood. This is highlighted as the major knowledge gaps in the Funding Opportunity Announcement (FOA) “Biology of Bladder Cancer (PAR-19-184)”: 1) “identifying biological mechanisms underlying disparities in sex in bladder cancer incidence”; and 2) “investigating the role of the microbiome in the bladder cancer biology”. The lack of understanding is due in part to the fact that the sex-biasing factors are often confounding co-variants. For example, the sex chromosomes are coupled with the sex hormones. Because of the confounding nature, the impacts of individual sex-biasing factors are exceedingly difficult to quantify. Gut microbiota differs significantly between sexes. Its potential sex- specific role in BCa remains unknown despite a preponderance of evidence that gut microbiota exerts the profound effects on cancer initiation, progression and therapy. To gain insight onto the sex differences in BCa, we will test the hypothesis that the gut microbiota plays a sex-specific role in regulating BCa incidence and mortality. To test this hypothesis, we have designed two specific aims using the innovative genetic and genomic strategies. First, we will determine whether the eradication of microbiota blunts the sex differences in BCa incidence and mortality; And second, we will identify gut microorganisms that are closely associated with BCa incidence and mortality. Upon conclusion, the proposal is expected to significantly advance our knowledge of the gender disparities in cancer and to identify candidate gut microbes that are tightly associated with BCa incidence and mortality.

男性患膀胱癌和死亡的可能性是女性的 3-5 倍，但潜在的因素人们对BCA中这些性别差异的机制知之甚少，这被强调为主要问题。资助机会公告 (FOA)“膀胱癌生物学 (PAR-19-184)”中的知识差距： 1) “确定膀胱癌发病率性别差异的生物学机制”；2) “调查微生物组在膀胱癌生物学中的作用”部分是由于缺乏了解。事实上，性别偏见因素常常是混淆的共变体，例如性染色体。由于混杂性，个体性别偏见的影响与性激素相关。肠道微生物群在性别之间存在显着差异。尽管有大量证据表明肠道微生物群发挥着对癌症发生、进展和治疗的广泛影响为了深入了解 BCa 的性别差异，我们将检验肠道微生物群在调节 BCa 发生率方面发挥性别特异性作用的假设，以及为了检验这一假设，我们利用创新的遗传和基因组设计了两个具体目标。首先，我们将确定消灭微生物群是否会减弱 BCa 的性别差异。发病率和死亡率；其次，我们将确定与 BCa 密切相关的肠道微生物结论得出后，该提案预计将大大提高我们对发病率和死亡率的认识。癌症中的性别差异并确定与 BCa 密切相关的候选肠道微生物发病率和死亡率。