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遗传多样性、近亲繁殖与癌症。

Genetic diversity, inbreeding and cancer.

机构信息

Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, Australia.

School of Biological Sciences, University of Tasmania, Private Bag 55, Hobart, Tasmania 7001, Australia.

出版信息

Proc Biol Sci. 2018 Mar 28;285(1875). doi: 10.1098/rspb.2017.2589.

Abstract

Genetic diversity is essential for adaptive capacities, providing organisms with the potential of successfully responding to intrinsic and extrinsic challenges. Although a clear reciprocal link between genetic diversity and resistance to parasites and pathogens has been established across taxa, the impact of loss of genetic diversity by inbreeding on the emergence and progression of non-communicable diseases, such as cancer, has been overlooked. Here we provide an overview of such associations and show that low genetic diversity and inbreeding associate with an increased risk of cancer in both humans and animals. Cancer being a multifaceted disease, loss of genetic diversity can directly (via accumulation of oncogenic homozygous mutations) and indirectly (via increased susceptibility to oncogenic pathogens) impact abnormal cell emergence and escape of immune surveillance. The observed link between reduced genetic diversity and cancer in wildlife may further imperil the long-term survival of numerous endangered species, highlighting the need to consider the impact of cancer in conservation biology. Finally, the somewhat incongruent data originating from human studies suggest that the association between genetic diversity and cancer development is multifactorial and may be tumour specific. Further studies are therefore crucial in order to elucidate the underpinnings of the interactions between genetic diversity, inbreeding and cancer.

摘要

遗传多样性对于适应能力至关重要,为生物体提供了成功应对内在和外在挑战的潜力。尽管在不同分类群中已经明确建立了遗传多样性与寄生虫和病原体抗性之间的相互关系,但遗传多样性因近亲繁殖而丧失对非传染性疾病(如癌症)的发生和发展的影响却被忽视了。在这里,我们提供了对这些关联的概述,并表明遗传多样性降低和近亲繁殖与人类和动物的癌症风险增加有关。由于癌症是一种多方面的疾病,遗传多样性的丧失可能会直接(通过积累致癌纯合突变)和间接(通过增加对致癌病原体的易感性)影响异常细胞的出现和免疫监视的逃逸。在野生动物中观察到的遗传多样性降低与癌症之间的联系可能会进一步危及许多濒危物种的长期生存,这凸显了在保护生物学中考虑癌症影响的必要性。最后,源于人类研究的有些不一致的数据表明,遗传多样性与癌症发展之间的关联是多因素的,并且可能因肿瘤而异。因此,为了阐明遗传多样性、近亲繁殖和癌症之间相互作用的基础,进一步的研究至关重要。

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