Department of Nutrition, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA.
Clin Exp Metastasis. 2010 May;27(5):279-93. doi: 10.1007/s10585-010-9326-z. Epub 2010 Mar 31.
Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer.
乳腺癌是一种复杂的疾病，由遗传和环境因素共同作用导致。在环境因素中，身体成分和特定膳食成分（如总脂肪）的摄入与乳腺癌发病率和转移的增加有关。我们之前的研究表明，高脂饮食喂养的小鼠比标准饮食喂养的小鼠具有更短的乳腺癌潜伏期、更大的肿瘤生长和更多的肺转移。随后的遗传分析确定了几种转移性乳腺癌的修饰基因，以及癌症修饰基因与膳食脂肪之间的广泛相互作用。为了阐明与饮食相关的乳腺癌和转移风险的遗传修饰基因，我们测量了来自乳腺肿瘤的全基因表达谱和拷贝数改变，并鉴定了表达数量性状基因座（eQTL）。与先前检测到的转移修饰基因共定位的功能候选基因被鉴定出来。其他分析，如与膳食脂肪相互作用分析、因果关系和数据库评估的 eQTL，有助于进一步细化候选基因座，产生一组潜在参与转移性乳腺癌发病机制的基因。
