Experiences of Discrimination, Dysbiosis, and Racial Disparities in Ovarian Cancer

摘要 2020年，超过21，000名女性被诊断患有卵巢癌（OC）。虽然有重大的 随着治疗的进展，OC的有效筛查仍然难以捉摸。女性更有可能表现出 晚期疾病，导致令人沮丧的五年生存率为48%。死亡率 黑人女性比例更高。有证据表明，这是多方面的贡献 尽管对社会经济和环境问题进行了广泛的调查， 决定因素，生物学对生存差异的贡献研究不足。因为癌症的差异 由于生物风险是多因素的，因此必须研究社会决定因素影响生物风险的机制 影响晚期OC的因素。遭受歧视的情况在以下群体中更为普遍： 黑人妇女和慢性炎症有关，这是晚期OC的危险因素。的 OC的更具侵袭性的亚型，包括高级别浆液性癌（HGSC），是由高水平的 生殖道发生在这个区域的炎症可能是阴道变化的直接结果 增加pH值和促进上行感染的微生物组。因此爆炸物处理的潜在途径 可能影响晚期OC的发展是通过阴道微生物组的失调， 这种现象被称为阴道生态失调。这项研究的中心论点是，心理社会压力次要 通过阴道生态失调导致晚期OC。这项研究将收集阴道 来自患有OC的黑人和白色妇女的微生物样本，并使用16 S rRNA测序。随后，我们建议进行深入的关联研究，评估 EOD、阴道微生态失调、OC分期和生存率之间的关系。R01资助的ORCHiD 研究将提供有关急性压力、社会经济和环境措施的广泛信息 因素以及诊断时的OC分期、治疗过程和生存随访。从这个研究结果 将指导未来的分析复合社会和生物学效应的心理社会压力对OC病因 和生存这项研究的结果对于理解社会和生物的相互作用至关重要。 OC差异机制。研究结果将为未来的临床干预试验提供信息，例如， 使用抗炎药物，作为一种潜在的战略，以减轻差距，在先进阶段的OC。

Abstract In 2020, over 21,000 women were diagnosed with ovarian cancer (OC). While there have been significant therapeutic advances, effective screening for OC remains elusive. Women are more likely to present with an advanced disease stage, contributing to the dismal five-year survival rate of 48%. Mortality is disproportionately higher among Black women. Evidence has shown a multi-dimensional contribution to this disparity and, while there has been extensive investigation into socioeconomic and environmental determinants, biological contribution to the survival disparity is understudied. Because cancer disparities are multifactorial, it is imperative to study the mechanisms through which social determinants impact biological risk factors that influence advanced-stage OC. Experiences of discrimination (EOD) are more prevalent among Black women and have been associated with chronic inflammation, a risk factor for advanced-stage OC. The more aggressive subtypes of OC, including high-grade serous carcinoma (HGSC), arise from high in the reproductive tract. Inflammation that occurs in this region may be the direct result of changes in the vaginal microbiome that increase pH and promote ascending infection. Therefore, a potential pathway by which EOD may influence development of advanced-stage OC is through dysregulation of the vaginal microbiome, a phenomenon known as vaginal dysbiosis. The central thesis of this study is that psychosocial stress secondary to EOD contributes to advanced-stage OC via vaginal dysbiosis. The proposed study will collect vaginal microbial samples from Black and White women with OC and characterize the microbial community using 16S rRNA sequencing. Subsequently, we propose to conduct an in-depth association study evaluating the relationships between EOD, vaginal dysbiosis, OC stage, and survival. The associated R01-funded ORCHiD study will provide extensive information on measures of acute stress, socioeconomic and environmental factors as well as OC stage at diagnosis, course of treatment, and survival follow-up. Findings from this study will direct future analysis of the compounded social and biological effect of psychosocial stress on OC etiology and survival. The results of this study are essential to understanding the interaction of social and biological mechanisms in OC disparity. Findings will inform future studies testing clinical interventions, for example, the use of anti-inflammatory medications, as a potential strategy to mitigate disparities in advanced-stage OC.