对癌症的遗传易感性:候选基因中的多形态的作用
Linda M Dong1, John D Potter, Emily White
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
JAMA
|May 29, 2008
概括
候选基因关联研究表明,近三分之一的基因变异癌症联系是显著的. 代谢酶的变异,如GSTM1,显示出与癌症风险的一致和强烈的关联.
科学领域:
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
- 流行病学 流行病学
背景情况:
- 基因定型和DNA采集方面的进步推动了遗传关联研究.
- 观察性研究越来越多地包含遗传数据.
研究的目的:
- 评估候选基因关联研究对理解癌症易感性的进展和影响.
- 评估这些研究对当前知识的贡献.
主要方法:
- 2008年3月之前发表的关于遗传多态度和癌症风险的元分析和聚合分析的系统综述.
- 纳入标准: >= 500例,癌症风险结果,排除HLA标志物,英语.
- 数据提取包括癌症部位,基因,变异,影响估计,置信区间和研究特征.
主要成果:
- 161个元分析评估了344个基因变异的癌症关联.
- 28% (98/344) 的关联是统计学上显著的 (P <.05).
- 在对错误阳性报告概率 (FPRP) 进行调整后,四个关键关联仍然值得注意,包括GSTM1无和膀癌,NAT2缓慢化剂和膀癌,MTHFR C677T和胃癌,以及GSTM1无和急性白血病.
结论:
- 近三分之一的候选基因变异癌症关联表明了统计学意义.
- 代谢酶编码基因的变异是最一致和最重要的发现之一.
- 特定的基因变异,如GSTM1 null,与某些癌症有着强大的关联.
相关概念视频
Cancer Prevention
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

