Hemminki Kari, Försti Asta, Lorenzo Bermejo Justo
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
J Carcinog. 2005 Jan 17;4(1):2. doi: 10.1186/1477-3163-4-2.
Single nucleotide polymorphisms (SNPs) are extensively used in case-control studies of practically all cancer types. They are used for the identification of inherited cancer susceptibility genes and those that may interact with environmental factors. However, being genetic markers, they are applicable only on heritable conditions, which is often a neglected fact. Based on the data in the nationwide Swedish Family-Cancer Database, we review familial risks for all main cancers and discuss the evidence for a heritable component in cancer. The available evidence is not conclusive but it is consistent in pointing to a minor heritable etiology in cancer, which will hamper the success of SNP-based association studies. Empirical familial risks should be used as guidance for the planning of SNP studies. We provide calculations for the assessment of familial risks for assumed allele frequencies and gene effects (odds ratios) for different modes of inheritance. Based on these data, we discuss the gene effects that could account for the unexplained proportion of familial breast and lung cancer. As a conclusion, we are concerned about the indiscriminate use of a genetic tool to cancers, which are mainly environmental in origin. We consider the likelihood of a successful application of SNPs in gene-environment studies small, unless established environmental risk factors are tested on proven candidate genes.
单核苷酸多态性(SNPs)在几乎所有癌症类型的病例对照研究中都被广泛使用。它们被用于识别遗传性癌症易感基因以及那些可能与环境因素相互作用的基因。然而,作为遗传标记,它们仅适用于遗传性疾病,而这一事实常常被忽视。基于瑞典全国性家庭癌症数据库中的数据,我们回顾了所有主要癌症的家族风险,并讨论了癌症中遗传成分的证据。现有证据并不确凿,但一致表明癌症存在轻微的遗传病因,这将阻碍基于SNP的关联研究的成功。经验性家族风险应用于指导SNP研究的规划。我们提供了针对不同遗传模式下假定等位基因频率和基因效应(比值比)的家族风险评估计算方法。基于这些数据,我们讨论了可能解释家族性乳腺癌和肺癌中无法解释部分的基因效应。总之,我们担心对主要由环境因素引起的癌症不加区分地使用遗传工具。我们认为,除非在已证实的候选基因上测试既定的环境风险因素,否则SNP在基因-环境研究中成功应用的可能性很小。