Hawaii Cancer Center, Honolulu, HI, USA.
MRC Toxicology Unit, Leicester, UK.
Cell Death Differ. 2018 Nov;25(11):1885-1904. doi: 10.1038/s41418-018-0213-5. Epub 2018 Oct 15.
The relative contribution of intrinsic genetic factors and extrinsic environmental ones to cancer aetiology and natural history is a lengthy and debated issue. Gene-environment interactions (G x E) arise when the combined presence of both a germline genetic variant and a known environmental factor modulates the risk of disease more than either one alone. A panel of experts discussed our current understanding of cancer aetiology, known examples of G × E interactions in cancer, and the expanded concept of G × E interactions to include somatic cancer mutations and iatrogenic environmental factors such as anti-cancer treatment. Specific genetic polymorphisms and genetic mutations increase susceptibility to certain carcinogens and may be targeted in the near future for prevention and treatment of cancer patients with novel molecularly based therapies. There was general consensus that a better understanding of the complexity and numerosity of G × E interactions, supported by adequate technological, epidemiological, modelling and statistical resources, will further promote our understanding of cancer and lead to novel preventive and therapeutic approaches.
内在遗传因素和外在环境因素对癌症病因学和自然史的相对贡献是一个漫长而有争议的问题。当一个种系遗传变异和一个已知的环境因素共同存在时,会出现基因-环境相互作用(GxE),从而使疾病的风险比单一因素的风险更高。一组专家讨论了我们目前对癌症病因学的理解、癌症中已知的 GxE 相互作用的例子,以及将 GxE 相互作用扩展到包括体细胞癌症突变和致癌治疗等医源性环境因素的新概念。特定的遗传多态性和基因突变会增加对某些致癌物质的易感性,并且可能在不久的将来针对新型基于分子的疗法针对癌症患者进行预防和治疗。专家们普遍认为,更好地理解 GxE 相互作用的复杂性和数量,辅以充足的技术、流行病学、建模和统计资源,将进一步促进我们对癌症的理解,并带来新的预防和治疗方法。