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

Abstract

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.

Suppression of Skeletal Muscle Turnover in Cancer Cachexia: Evidence from the Transcriptome in Sequential Human Muscle Biopsies

“…These findings are consistent with our suggestion that removal of cancer allows skeletal muscle to recover from net catabolism. We have recently published data detailing a role for ADIPOQ, upregulated at baseline, as a network hub in cachexia (46) suggesting that this might have a role in cancer-associated muscle atrophy or be a sensitive integrator of the net underlying processes (e.g., metabolic status of the muscle). Increased expression of the phosphoenolpyruvate carboxykinase 1 (PCK1) gene has been found in lean rodents (47) in which it has been linked to increased endurance capacity.…”

Influence of body composition profile on outcomes following colorectal cancer surgery

“…Skeletal muscle is one of the most modifiable human tissues. Changes in skeletal muscle occur for numerous reasons, including inflammation, age, and nutritional and chronic disease factors 6 . To indicate the presence of clinically relevant muscle wasting, irrespective of illness and age, Fearon and colleagues 7 proposed the term myopenia (mys in Greek is muscle) in 2011.…”

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

“…Thus, in different patients, the same tumor type may or may not lead to cachexia and, when the syndrome occurs, it can be of different severity, thus suggesting some type of individual factor involved in the progression of the disease. [1] Cancer patients with cachexia show a reduced response to chemoradiotherapy [2] and a poor prognosis. [3] Since up to 20% of all cancer deaths are caused directly by cachexia through immobility and cardiac respiratory failure, [4][5][6] it could be very important for physicians treating cancer patients to act at a very early stage of the disease and to know whether a patient will or will not develop cachexia and its degree of severity.…”