剑桥大学和爱丁堡大学的研究人员通过小鼠实验首次直接证明，遗传基因在决定癌症风险中起到关键作用[1]。研究表明，继承的遗传变异与获得性遗传突变相互作用，共同影响肿瘤的演化路径[1]。这项发现发表于2026年7月22日的《自然》杂志，为癌症预防和筛查策略的发展提供了新的方向[1]。
研究团队在遗传易感性不同的四种小鼠品系中开展实验，这些品系的遗传多样性水平与人群相当[1]。所有小鼠在相同条件下于15天龄时接受单一剂量的肝致癌物DEN（二乙基亚硝胺），之后研究人员对近600个肿瘤的基因组进行了测序[1]。
结果显示，尽管所有小鼠品系的癌症几乎都获得了激活MAPK通路（一种多步级联信号系统）的驱动突变，但不同遗传背景的小鼠表现出明显不同的突变过程和全基因组重复倾向[1]。这表明即使面临相同的致癌刺激，遗传背景也会显著影响肿瘤的发展方式[1]。
该研究由英国癌症研究基金会、医学研究委员会、欧洲研究委员会和韦尔科姆信托基金主要资助[1]。
Researchers have directly demonstrated for the first time through mouse studies that inherited genetic variations play a critical role in determining cancer risk when combined with acquired mutations. [1] The study, published in Nature on July 22, 2026, reveals how the interaction between germline genetic variants and somatic mutations shapes the evolutionary trajectory of tumors. [1]
Scientists conducted experiments across four genetically distinct mouse strains with diversity levels comparable to human populations. [1] All mice received a single dose of the liver carcinogen DEN (diethylnitrosamine) at 15 days of age under identical conditions. [1] Researchers then sequenced the genomes of nearly 600 tumors to track how cancer developed. [1] While all mouse strains acquired driving mutations that activated the MAPK pathway—a multi-step signaling cascade—across their cancer cases, the different genetic backgrounds resulted in distinct mutation processes and varying genome-wide duplication patterns. [1]
The findings suggest that individual genetic predisposition significantly influences not just whether DNA damage leads to cancer, but also how tumors evolve at the molecular level. This work, supported primarily by Cancer Research UK, the Medical Research Council, the European Research Council, and the Wellcome Trust, points toward the need for future cancer prevention and screening strategies that take genetic background and population diversity into greater account. [1]