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.

男性因膀胱癌（BCA）的发展和死亡的可能性是女性的3-5倍这些性别分布在BCA中的机制知之甚少。这被强调为专业资金机会公告（FOA）中的知识差距“膀胱癌的生物学（PAR-19-184）”： 1）“确定膀胱癌事件中性别差异的生物学机制”；和2） “研究微生物组在膀胱癌生物学中的作用”。缺乏理解是部分原因事实是，性偏见的因素通常是混淆的共同变化。例如，性染色体与性马相结合。由于性质的混杂，个人性偏见的影响因素很难量化。性别之间的肠道微生物群显着差异。它的潜在性别 - 在BCA中的具体作用仍然未知目的地，肠道微生物群执行的大量证据对癌症开始，进展和治疗的深远影响。为了深入了解BCA的性别差异，我们将检验以下假设：肠道菌群在调节BCA发生率和死亡。为了检验这一假设，我们使用创新的遗传和基因组设计了两个特定目标策略。首先，我们将确定消除微生物群是否会钝化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发病率和死亡率。总而言之，该提议有望大大提高我们对癌症中的性别分布并确定与BCA紧密相关的候选肠道微生物发病率和死亡率。