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用于改善肾癌、前列腺癌和膀胱癌健康差异结果的新兴基因组生物标志物。

Emerging genomic biomarkers for improving kidney, prostate, and bladder cancer health disparities outcomes.

作者信息

Mitchell Khadijah A, Williams Heinric

机构信息

Biology Department, Lafayette College, Easton, PA.

Urology Department, Geisinger Clinic, Danville, PA; Weis Center for Research, Geisinger Clinic, Danville, PA.

出版信息

Urol Oncol. 2022 Apr;40(4):126-132. doi: 10.1016/j.urolonc.2019.04.024. Epub 2019 Jun 23.

Abstract

BACKGROUND

Recent advances in genomic and genetic technologies have facilitated better health outcomes for urologic cancer patients. Genomic and genetic heterogeneity may contribute to differences in tumor biology and urologic cancer burden across various populations.

OBJECTIVE

To examine how emerging genomic and genetic biomarkers, self-reported race, and ancestry-informative markers are associated with kidney, prostate, and bladder cancer outcomes.

RESULTS

Genomic and genetic alterations found in African American kidney cancer patients included distinct somatic mutations, somatic copy number alterations, chromosomal instability, germ-line risk alleles, and germ-line genetic variants. These changes correlated with improved risk prediction, prognosis, and survival; and a predicted decrease in response to targeted therapies. SNP risk alleles and ancestry-informative markers were associated with improved risk prediction in prostate cancer patients of both African and European descent. AKT activation suggest differential response to AKT-targeted therapies in African American, Asian American, and Tunisian bladder cancer patients. Both self-reported race and genetic ancestry predicted urologic cancer risk prediction.

CONCLUSION

Precision medicine approaches that integrate population-specific genomic and genetic information with other known urologic cancer-specific characteristics can improve outcomes and be leveraged to reduce cancer health disparities. Further investigations are necessary to identify novel genomic biomarkers with clinical utility.

摘要

背景

基因组学和基因技术的最新进展为泌尿生殖系统癌症患者带来了更好的健康结局。基因组和基因异质性可能导致不同人群中肿瘤生物学特性和泌尿生殖系统癌症负担的差异。

目的

研究新兴的基因组和基因生物标志物、自我报告的种族以及祖先信息标记物与肾癌、前列腺癌和膀胱癌结局之间的关联。

结果

在非裔美国肾癌患者中发现的基因组和基因改变包括独特的体细胞突变、体细胞拷贝数改变、染色体不稳定性、种系风险等位基因和种系基因变异。这些变化与风险预测、预后和生存率的改善相关;并且预测对靶向治疗的反应会降低。单核苷酸多态性(SNP)风险等位基因和祖先信息标记物与非洲裔和欧洲裔前列腺癌患者的风险预测改善相关。AKT激活提示非裔美国、亚裔美国和突尼斯膀胱癌患者对AKT靶向治疗的反应存在差异。自我报告的种族和基因祖先都可预测泌尿生殖系统癌症风险。

结论

将特定人群的基因组和基因信息与其他已知的泌尿生殖系统癌症特异性特征相结合的精准医学方法可以改善结局,并可用于减少癌症健康差异。有必要进一步开展研究以鉴定具有临床应用价值的新型基因组生物标志物。

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