Aggressive colorectal cancer subtypes and social disadvantage in a racially diverse cohort

摘要 虽然在过去几十年中，结直肠癌（CRC）的总体发病率和死亡率有所下降， 非裔美国人（AA）的CRC发病率和死亡率继续高于非西班牙裔白人 （NHW）。共有CRC分子肿瘤亚型是致癌途径的重要指标， 预后，与特定体细胞基因突变相关的区域，错配修复（MMR）表型， 基因特异性甲基化，尽管目前尚不清楚这些亚型中的种族差异 CRC生存率的种族差异的基础，因为这些亚型来自主要由以下组成的研究 NHW CRC。遗传、行为和环境因素对CRC相关性的相对贡献 AA个体的结果在很大程度上仍然未知，迫切需要有关 发病机制，以改善筛选和治疗的方法。对于区域一级来说尤其如此 社会经济因素，如收入和住房价值，与CRC的高风险有关，但 其生物学后果尚不清楚。这项研究的总体目标是确定基因组和 在一个特征明确的AA CRC病例队列中，与CRC发病机制相关的社会因素。我们 假设肿瘤生物学，这里定义为肿瘤中的体细胞和表观遗传改变，解释了 CRC结果中的种族差异占很大比例，地区因素改变了这种关系。 我们的长期目标是通过一个全面的， 了解不同人群中出现的肿瘤分子事件。

ABSTRACT While overall colorectal cancer (CRC) incidence and mortality have declined over the last several decades, CRC incidence and mortality rates continue to be higher in African Americans (AAs) than non-Hispanic Whites (NHW). Consensus CRC molecular tumor subtypes are important indicators of carcinogenic pathway and prognosis, and area associated with specific somatic gene mutations, mismatch repair (MMR) phenotype, and gene-specific methylation, although it is currently unknown whether racial differences in these subtypes underlie racial disparities in CRC survival as these subtypes were derived from studies largely comprised of NHW CRCs. The relative contributions of genetic, behavioral and environmental factors on CRC-related outcomes in AA individuals remain largely unknown and there is a critical need for information about pathogenesis to improve approaches to screening and treatment. This is especially true for area-level socioeconomic factors, such as income and housing values, that are associated with higher risk of CRC but for which the biologic consequences are not yet known. The overall goal of the study is to identify genomic and social factors associated with CRC pathogenesis in a well-characterized cohort of AA CRC cases. We hypothesize that tumor biology, here defined by somatic and epigenetic alterations in tumors, explains a substantial proportion of the racial disparities in CRC outcomes, and area-level factors modify this relationship. Our long-term goal is to improve our ability to diagnose, treat and prevent CRC through a comprehensive understanding of the molecular events in tumors that arise in diverse populations.