Methodological and molecular factors underlying racial disparities in cancer outcomes

项目摘要/摘要 尽管癌症存活率有所提高，但男性和女性的种族差异依然存在。虽然 黑人女性的总体发病率低于白人女性，死亡率更高；相比之下，黑人男性 有更高的发病率和死亡率。乳腺癌和卵巢癌，这两者都是导致这种不和谐的原因 在女性中，是由激素驱动的癌症，具有重叠的遗传、分子和生活方式风险因素。在……里面 2020年，乳腺癌导致40,000多人死亡，而卵巢癌占近15,000人。 可归因于这些癌症的死亡在黑人女性中不成比例地发生。死亡率的差异是 在最初诊断为非转移性疾病的患者中最为明显。在这些患者中， 癌症复发是癌症特有死亡的必要先兆。然而，复发率很低。 由于缺乏系统收集的以人口为基础的数据，因此无法理解。当前对复发的估计 风险基于临床试验数据、基于诊所的注册或使用管理声明的算法，以及 因此，它们不能代表所有患者，特别是那些较少获得专门试验或诊所的患者。 准确的基于人群的复发估计对于充分了解死亡率差异至关重要。一个 基于人群估计的重要方法学考虑是对癌症幸存者的随访 在最初诊断数年后。此前的研究表明，少数族裔患者更有可能走失 为了后续行动，偏向于特定种族的估计。本项目的目标1将调查损失差异如何 利用佐治亚州丰富的资源，针对特定种族的后续偏见，基于人口的复发估计 癌症登记处(GCR)，这是一个以人口为基础的登记处，位于一个种族多元化的大州。GCR是第一个 以人群为基础的癌症登记系统地识别和登记乳腺癌复发 幸存者。AIMS 2和3将使用现有的流行病学研究来调查患者层面的驱动因素 不同之处。目的2将研究肿瘤细胞中雄激素受体与乳房的关系 绝经前妇女的癌症复发，特别是那些具有侵袭性亚型的妇女 对可用的内分泌治疗有反应，而且在黑人女性中更常见的诊断。目标3将 调查更年期激素治疗的作用，以及这种暴露对治疗的中介作用。 卵巢癌进展中的因素，这一关联只在白人女性中进行了研究。结果 这项研究将为准确估计基于人群的复发率提供一个框架， 对导致乳腺癌和卵巢癌预后种族差异的其他因素的进一步洞察，并将 为未来旨在减少不平等现象的研究提供信息。此外，该奖学金将提供一系列丰富的 流行病学培训、研究和职业发展将有助于候选人成为 成功和独立的癌症研究人员，具有广泛的流行病学知识和技能 方法，熟悉癌症护理的临床基础，以及对癌症差异的了解。

Project Summary/Abstract Despite improvements in cancer survival, racial disparities have persisted for both men and women. Although overall incidence is lower among Black women than White women, mortality is greater; in contrast Black men have both greater incidence and mortality. Breast and ovarian cancers, which both contribute to the incongruity among women, are hormonally-driven cancers with overlapping genetic, molecular, and lifestyle risk factors. In 2020, breast cancer was the cause of over 40,000 deaths, while ovarian cancer accounted for nearly 15,000. Deaths attributable to these cancers occur disproportionately among Black women. Disparities in mortality are most pronounced among patients initially diagnosed with non-metastatic disease. Among these patients, cancer recurrence is a necessary precursor to a cancer-specific death. However, recurrence is poorly understood due to the lack of systematically-collected population-based data. Current estimates of recurrence risk are based on clinical trial data, clinic-based registries, or algorithms using administrative claims, and therefore are not representative of all patients, particularly those with less access to specialized trials or clinics. Accurate population-based estimation of recurrence is critical to fully understand mortality disparities. An important methodological consideration in population-based estimation is the follow-up of cancer survivors years after initial diagnosis. Previous studies have suggested racial minority patients are more likely to be lost to follow-up, biasing race-specific estimates. Aim 1 of this project will investigate how differences in loss to follow-up bias race-specific, population-based recurrence estimates, using the rich resources of the Georgia Cancer Registry (GCR), a population-based registry in a large, racially diverse state. The GCR is the first population-based cancer registry to systematically identify and register recurrences among breast cancer survivors. Aims 2 and 3 will use existing epidemiologic studies to investigate patient-level drivers underlying the disparities. Aim 2 will investigate the association between androgen receptor in tumor cells and breast cancer recurrence among premenopausal women, particularly those with aggressive subtypes that do not respond to available endocrine therapy and that are more commonly diagnosed in Black women. Aim 3 will investigate the role of menopausal hormone treatment, and the mediating effects of this exposure on treatment factors, in ovarian cancer progression, an association that has only been examined in White women. Results from this research will provide a framework for accurate estimation of population-based recurrence rates, additional insight into factors contributing to racial disparities in breast and ovarian cancer outcomes, and will inform future studies aimed at reducing inequities. In addition, the fellowship will provide a rich array of epidemiologic training, research, and career development that will contribute to the candidate’s ability to be a successful and independent cancer researcher, with knowledge and skills in a broad array of epidemiologic methods, familiarity with the clinical underpinnings of cancer care, and understanding of cancer disparities.