Approved research

Deciphering the genetics of cachexia

Lay summary

Cachexia and cancer-associated cachexia (CAC) are characterized by extensive body weight loss, loss of fat tissue (white adipose tissue), and skeletal muscle. In cancer patients, CAC is a positive risk factor for death. The molecular mechanisms underlying cachexia and CAC are currently only poorly understood, thus limiting therapeutic intervention. Our laboratory has evidence that cachexia and CAC have an underlying genetic component, and we propose to perform a genome-wide association study (GWAS) to uncover the genetic underpinnings of cachexia/CAC in the context of cancer, infectious and inflammatory disease with the help of genotype and phenotype data from the UK Biobank. Cachexia and especially cancer-associated cachexia (CAC) is characterized by extensive body weight loss, loss of fat tissue, and skeletal muscle, and other phenotypes including wide-spread inflammation. CAC occurs in approx. 50% of cancer patients, depending on its definition, and is an independent predictor for cancer-related death (PMID:21296615). We envision our project will yield novel insights into the biological mechanisms of cachexia in the context of cancer, infectious and inflammatory disease. Validation of our findings could pave the way for cachexia/CAC intervention strategies, and results of our health-related research study is thus of relevance for patients and the public in general. We aim to identify genetic markers associated with rapid weight loss in individuals diagnosed with cancer, infectious and inflammatory disease to obtain novel insights into cachexia and especially CAC. For this, we will perform an unbiased genome-wide association study to identify association between patients? genotype and weight loss. Weight changes will be determined using weight assessment at repeated timepoints and/or adipose tissue changes as determined by imaging. We propose to pursue our analyses with the full cohort currently available, limited to patients with cancer, infectious and inflammatory disease for which genotyping data are available. We will include in our analysis cancer types with an incidence of at least 50 across the UK Biobank cohort (including colorectal cancer and pancreatic cancer), inflammation-related diseases with an incidence of at least 50 across the UK Biobank cohort (including chronic kidney disease, cystic fibrosis, multiple sclerosis, and Rheumatoid arthritis), and infectious diseases (including tuberculosis, HIV) with an incidence of at least 50 across the UK Biobank cohort.