Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review

Journal of genetics

Benjamin H. L. Tan1²  Frank Skorpen²  Kenneth C. H. Fearon²  Stein Kaasa¹  European Palliative Care Research Collaborative¹  James A. Ross² 

[1] Clinical Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim N-7006, Norway$$;Clinical and Surgical Sciences (Surgery), Royal Infirmary, University of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK$$

关键词: human genetics;    polymorphisms;    cachexia;   

DOI  :  

学科分类：生物科学（综合）

来源: Indian Academy of Sciences

【 摘 要 】

Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986–2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

【 授权许可】

Unknown