拉丁美洲人的基因血统与癌症

Alejandro Ruíz-Patiño, Leonardo Rojas, Jairo Zuluaga, Oscar Arrieta, Luis Corrales, Claudio Martín, Sandra Franco, Luis Raez, Christian Rolfo, Natalia Sánchez, Andrés Felipe Cardona
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摘要

拉美人口的特点是欧洲、美洲原住民(NA)、亚洲和非洲血统的祖先混杂在一起,形成了错综复杂的混血模式,导致了庞大而复杂的遗传景观,蕴藏着独特的新型变异组合。这种遗传多样性不仅对传统的群体遗传学方法提出了挑战,也为深入了解其对健康的影响开辟了途径。在癌症方面,遗传血统、生活方式因素和医疗保健差异之间的相互作用,为拉丁美洲不同亚人群的不同发病率和死亡率增添了一层复杂性。大量研究揭示了这种复杂的相互依存关系,无论是对居住在拉美大陆还是国外的拉美患者进行的研究,都揭示了影响不同疾病表型的种系组成的明显差异,如 Luminal B 和 Her2 乳腺肿瘤、表皮生长因子受体(EGFR)和 KRAS 突变的肺腺癌的发病率较高,此外还有 BRCA1/2 致病变体的富集,以及 APC 和 MLH1 等结直肠癌相关基因变体的发病率高于预期。前列腺癌的新型风险变异也仅在拉丁美洲人群中发现。由于遗传差异的复杂性,来自每个人祖先的输入似乎在这些复杂疾病表型的发展过程中起着相互影响的独立作用。通过了解这些独特的人群特征,基因组祖先为定制预后评估和优化肿瘤干预措施提供了一条很有前景的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genomic ancestry and cancer among Latin Americans

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

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