Risch Angela, Plass Christoph
German Cancer Research Center, Division of Epigenomics and Cancer Risk Factors, Heidelberg, Germany.
Int J Cancer. 2008 Jul 1;123(1):1-7. doi: 10.1002/ijc.23605.
Lung cancer is the leading cause of cancer-related death and thus a major health problem. The efficiency of current treatment modalities for lung cancer depends strongly on the time of diagnosis, with better chances of survival if a tumor has been detected at an early stage. Thus, there is an urgent need for rapid and efficient early detection methods. Biomarkers represent a possible alternative to current, rather expensive, screening tools such as spiral computer tomography (CT), or may allow the identification of high risk groups for whom screening would be cost efficient. Although most lung cancers are the consequence of smoking, a substantial fraction of molecular-epidemiological studies point to high-prevalence, low-penetrance genetic polymorphisms as modifiers of environmental lung cancer risk. In the past the genomics field has also made significant advances in identifying genetic lesions that can now be harvested with the goal of identifying novel biomarkers for lung cancer. Furthermore, the importance of epigenetic changes that occur during lung cancer development has been reported, but has been underestimated in the past. Novel high-throughput, quantitative assays for the detection of DNA methylation or histone tail modifications are now applied, to search for alterations in the lung cancer genome and will identify novel cancer-related genes that may become attractive targets for treatment, provide new insight into the biology of lung cancers, and could also become useful biomarkers for the early detection of lung cancer in sputum, or may be used as prognostic markers. Thus, an integrative approach in lung cancer research combining epidemiological, genetic and epigenetic information becomes an important concept for the future.
肺癌是癌症相关死亡的主要原因,因此是一个重大的健康问题。当前肺癌治疗方式的有效性在很大程度上取决于诊断时间,如果肿瘤在早期被检测到,生存几率会更高。因此,迫切需要快速有效的早期检测方法。生物标志物可能是当前诸如螺旋计算机断层扫描(CT)等较为昂贵的筛查工具的替代方法,或者可以用于识别那些筛查具有成本效益的高危人群。虽然大多数肺癌是吸烟的后果,但相当一部分分子流行病学研究指出,高患病率、低外显率的基因多态性是环境性肺癌风险的修饰因素。过去,基因组学领域在识别基因损伤方面也取得了重大进展,现在可以收集这些基因损伤以识别肺癌的新型生物标志物。此外,肺癌发生过程中表观遗传变化的重要性已被报道,但过去一直被低估。现在应用新型高通量定量检测方法来检测DNA甲基化或组蛋白尾部修饰,以寻找肺癌基因组中的改变,并将识别出可能成为有吸引力治疗靶点的新型癌症相关基因,为肺癌生物学提供新的见解,还可能成为痰液中肺癌早期检测的有用生物标志物,或用作预后标志物。因此,将流行病学、遗传和表观遗传信息相结合的肺癌研究综合方法成为未来的一个重要概念。