利用人类遗传学开发癌症化学预防--机不可失。

Ulrike Peters, Ian Tomlinson
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摘要

大规模的基因研究正在可靠地确定普通人群中的许多疾病风险因素。其中一些遗传风险因素编码了潜在的药物靶点,遗传学已经帮助推出了治疗某些疾病的靶向药物,例如降低心血管疾病发病率的降脂药物。基于体细胞突变和基因组学,已经开发出多种治疗癌症的药物,但与此形成鲜明对比的是,人们似乎并不愿意利用种系遗传数据来开发预防恶性肿瘤的药物,尽管有大量的人可以从中受益,降低癌症发病率的潜力也很大,而且目前广泛使用非药物措施来减少癌症风险因素,如烟草、酒精和传染病。我们认为,当务之急是根据遗传学,包括受常见多态性影响的、可调节癌症风险的基因,开展协调一致的癌症预防工作。基于人类种系遗传学开发新型化学预防癌症靶向药物的机会巨大,但却未得到充分利用。这些工作可能需要国家和国际机构提供专项资金支持。参见 Winham 和 Sherman 的相关评论,第 13 页。
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Utilizing Human Genetics to Develop Chemoprevention for Cancer-Too Good an Opportunity to be Missed.

Large-scale genetic studies are reliably identifying many risk factors for disease in the general population. Several of these genetic risk factors encode potential drug targets, and genetics has already helped to introduce targeted agents for some diseases, an example being lipid-lowering drugs to reduce the incidence of cardiovascular disease. Multiple drugs have been developed to treat cancers based on somatic mutations and genomics, but in stark contrast, there seems to be a reluctance to use germline genetic data to develop drugs to prevent malignancy, despite the large numbers of people who could benefit, the potential for lowering cancer rates, and the widespread current use of non-pharmaceutical measures to reduce cancer risk factors such as tobacco, alcohol, and infectious diseases. We argue that concerted efforts for cancer prevention based on genetics, including genes influenced by common polymorphisms that modulate cancer risk, are urgently needed. There are enormous, yet underutilized, opportunities to develop novel targeted agents for chemoprevention of cancer based on human germline genetics. Such efforts are likely to require the support of a dedicated funding program by national and international agencies. See related commentary by Winham and Sherman, p. 13.

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