Biomarkers of genetic damage for cancer epidemiology
Biomarkers of genetic damage for cancer epidemiology
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DOI：
10.1016/s0300-483x(02)00480-8
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发表时间：
2002-12-27
期刊：
影响因子：
4.5
通讯作者：
Fenech, M
中科院分区：
文献类型：
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作者：
Fenech, M
癌症是一种基因表达改变的疾病，涉及一系列复杂的表观遗传事件、基因突变、染色体重排和染色体数目改变。遗传毒性事件与诱发癌症的巧合激发了人们对分子/细胞遗传学流行病学研究的极大兴趣，这些研究旨在将DNA修复和致癌物代谢基因的多态性以及DNA/染色体损伤的生物标志物与癌症风险联系起来。这些研究现在正在扩展到包括已知在DNA代谢和修复中重要的饮食因素的作用，如叶酸，维生素B12和锌。使用DNA损伤生物标志物作为癌症的替代物将极大地促进我们识别癌症最重要的风险因素的能力，然而这些生物标志物需要验证。北欧和意大利前瞻性队列研究证实，淋巴细胞染色体畸变率升高可预测癌症风险，目前正在进行类似研究，以验证其他生物标志物，如微核试验，这些生物标志物在更大的人群环境中更实用。这些生物标志物的验证需要彻底了解方法学、人口统计学、环境和饮食变量的重要性，正在进行的HUMN项目是如何实现微核试验的一个很好的例子。研究人类群体的能力为确定可接受的DNA损伤率和为基因组稳定性确定推荐的膳食摄入量提供了新的机会。将DNA损伤率控制在可能的最低限度可能对预防癌症和其他与DNA损伤相关的退行性疾病（包括衰老）产生重要影响。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Cancer is a disease of altered gene expression involving a complex array of epigenetic events, gene mutation, chromosome rearrangements and altered chromosome number. The coincidence of genotoxic events with the induction of cancer has fuelled great interest in molecular/cytogenetic epidemiological studies aimed at linking polymorphisms in genes for DNA repair and carcinogen metabolism and biomarkers of DNA/chromosome damage with cancer risk. These studies are now being expanded to include the role of dietary factors that are known to be important in DNA metabolism and repair such as folic acid, vitamin B12 and zinc. The use of DNA damage biomarkers as a surrogate for cancer would greatly facilitate our capacity to identify the most important risk factors for cancer however these biomarkers need validation. The Nordic and Italian prospective cohort studies have confirmed that elevated rates of chromosome aberrations in lymphocytes are predictive of cancer risk and similar studies are now underway to validate other biomarkers such as the micronucleus assay which are more practical to apply in the larger population setting. Validation of these biomarkers requires a thorough understanding of the importance of methodological, demographic, environmental and dietary variables and the ongoing HUMN project is a good example how this can be achieved for the micronucleus assay. The capacity to study human populations has opened up new opportunities to define acceptable DNA damage rates and to establish recommended dietary allowances for genomic stability. Controlling DNA damage rate to its possible minimum is likely to have an important impact in preventing cancer and other DNA damage-related degenerative diseases including ageing. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.