Teugels Erik, De Brakeleer Sylvia
Molecular Oncology, Faculteit Geneeskunde en Farmacie, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, 1090 Belgium.
NPJ Breast Cancer. 2017 Apr 17;3:13. doi: 10.1038/s41523-017-0017-7. eCollection 2017.
While environmental factors can greatly increase cancer risk, it is clear that an individual's genetic constitution has strong impact on tumor formation. Hereby we present an alternative cancer predisposition model built on the assumption that efficiencies of DNA maintenance mechanisms in normal cells are similar but not identical for each person. Small variations in an individual's genetic constitution may result in slightly increased genomic instability and generate typical mutational signatures in normal cells. With recent and expected advances in the next-generation sequencing field, qualitative and quantitative establishment of such mutational signatures in normal tissue must become feasible, and may meanwhile provide a more accurate estimation of individual cancer risks, even in persons without familial antecedents. An additional advantage of this approach is that cancer risk assessment will not strictly rely on the individual's genetic identity, but will also consider other factors (e.g., environmental and age) that can affect genomic integrity.
虽然环境因素会大大增加患癌风险，但很明显个体的基因构成对肿瘤形成有很大影响。在此，我们提出一种替代性的癌症易感性模型，该模型基于这样的假设：正常细胞中DNA维持机制的效率对每个人来说相似但并不完全相同。个体基因构成的微小差异可能导致基因组不稳定性略有增加，并在正常细胞中产生典型的突变特征。随着下一代测序领域近期及预期的进展，在正常组织中定性和定量建立此类突变特征必定会变得可行，同时这也可能更准确地评估个体患癌风险，即使对于没有家族病史的人也是如此。这种方法的另一个优点是，癌症风险评估将不会严格依赖个体的基因身份，还会考虑其他可能影响基因组完整性的因素（如环境和年龄）。
