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结直肠癌临床病理和分子肿瘤特征的种族差异:系统评价。

Racial disparities in colorectal cancer clinicopathological and molecular tumor characteristics: a systematic review.

机构信息

Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

School of Medicine and Public Health, Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.

出版信息

Cancer Causes Control. 2024 Feb;35(2):223-239. doi: 10.1007/s10552-023-01783-y. Epub 2023 Sep 9.

Abstract

PURPOSE

African Americans have the highest colorectal cancer (CRC) mortality of all racial groups in the USA, which may relate to differences in healthcare access or advanced stage at diagnosis. Recent evidence indicates that differences in tumor characteristics may also underlie disparities in mortality. To highlight recent findings and areas for investigation, we completed the first systematic review of racial disparities in CRC tumor prognostic markers, including clinicopathological markers, microsatellite instability (MSI), oncogene mutations, and novel markers, including cancer stem cells and immune markers.

METHODS

Relevant studies were identified via PubMed, limited to original research published within the last 10 years. Ninety-six articles were identified that compared the prevalence of mortality-related CRC tumor characteristics in African Americans (or other African ancestry populations) to White cases.

RESULTS

Tumors from African ancestry cases are approximately 10% more likely to contain mutations in KRAS, which confer elevated mortality and resistance to epidermal growth factor receptor inhibition. Conversely, African Americans have approximately 50% lower odds for BRAF-mutant tumors, which occur less frequently but have similar effects on mortality and therapeutic resistance. There is less consistent evidence supporting disparities in mutations for other oncogenes, including PIK3CA, TP53, APC, NRAS, HER2, and PTEN, although higher rates of PIK3CA mutations and lower prevalence of MSI status for African ancestry cases are supported by recent evidence. Although emerging evidence suggests that immune markers reflecting anti-tumor immunity in the tumor microenvironment may be lower for African American cases, there is insufficient evidence to evaluate disparities in other novel markers, cancer stem cells, microRNAs, and the consensus molecular subtypes.

CONCLUSION

Higher rates of KRAS-mutant tumors in in African Americans may contribute to disparities in CRC mortality. Additional work is required to understand whether emerging markers, including immune cells, underlie the elevated CRC mortality observed for African Americans.

摘要

目的

非裔美国人的结直肠癌(CRC)死亡率在美国所有种族群体中最高,这可能与医疗保健机会或诊断时的晚期阶段有关。最近的证据表明,肿瘤特征的差异也可能是导致死亡率差异的原因。为了突出最近的发现和研究领域,我们首次对 CRC 肿瘤预后标志物的种族差异进行了系统综述,包括临床病理标志物、微卫星不稳定性(MSI)、癌基因突变和新标志物,包括癌症干细胞和免疫标志物。

方法

通过 PubMed 确定相关研究,仅限于过去 10 年内发表的原始研究。确定了 96 篇比较非裔美国人(或其他非洲裔人群)CRC 肿瘤特征与白人病例与死亡率相关的患病率的文章。

结果

非洲裔病例的肿瘤中 KRAS 突变的可能性大约高出 10%,这会增加死亡率并对表皮生长因子受体抑制产生耐药性。相反,非洲裔美国人 BRAF 突变肿瘤的可能性大约低 50%,BRAF 突变肿瘤发生的频率较低,但对死亡率和治疗耐药性的影响相似。支持其他癌基因(包括 PIK3CA、TP53、APC、NRAS、HER2 和 PTEN)突变存在差异的证据不太一致,尽管最近的证据支持非洲裔病例中 PIK3CA 突变率较高和 MSI 状态较低的情况。尽管有新的证据表明,肿瘤微环境中反映抗肿瘤免疫的免疫标志物在非裔美国人病例中可能较低,但尚无足够的证据来评估其他新型标志物、癌症干细胞、microRNAs 和共识分子亚型的差异。

结论

非洲裔美国人中 KRAS 突变肿瘤的比例较高可能导致 CRC 死亡率的差异。需要进一步研究以了解是否包括免疫细胞在内的新兴标志物是导致非裔美国人 CRC 死亡率升高的原因。

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