P-selectin genotype is associated with the development of cancer cachexia

Publication

P-selectin genotype is associated with the development of cancer cachexia

Journal Paper/Review - Apr 4, 2012

Tan Benjamin H L, Fearon Kenneth C H, Skorpen Frank, Baracos Vickie E, Marks Daniel L, Kaasa Stein, Ross James A, Damaraju Sambasivarao, Solheim Tora S, Skipworth Richard J E, Deans D A Christopher, Strasser Florian, Viganò Antonio, Braun Theodore P, Fladvad Torill, European Palliative Care Research Collaborative

Citation

Tan B, Fearon K, Skorpen F, Baracos V, Marks D, Kaasa S, Ross J, Damaraju S, Solheim T, Skipworth R, Deans D, Strasser F, Viganò A, Braun T, Fladvad T, European Palliative Care Research Collaborative. P-selectin genotype is associated with the development of cancer cachexia. EMBO Mol Med 2012; 4:462-71.

Type

Journal Paper/Review (English)

Journal

EMBO Mol Med 2012; 4

Publication Date

Apr 4, 2012

Issn Electronic

1757-4684

Pages

462-71

Brief description/objective

The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C-reactive protein, > 10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n = 101) of cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP) SNP was found to be associated with weight loss >10% both in the discovery study (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29-0.93; p = 0.026) and the validation study (OR 0.09, 95% CI 0.01-0.98, p = 0.035). In separate studies, induction of muscle atrophy gene expression was investigated using qPCR following either tumour-induced cachexia in rats or intra-peritoneal injection of lipopolysaccharide in mice. P-selectin was found to be significantly upregulated in muscle in both models. Identification of P-selectin as relevant in both animal models and in cachectic cancer patients supports this as a risk factor/potential mediator in cachexia.