title: P-selectin genotype is associated with the development of cancer cachexia.
abstract: 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.
authors.affiliation: University of Edinburgh, Clinical and Surgical Sciences (Surgery), Royal Infirmary, Edinburgh, UK.
authors.forename: Benjamin H L
authors.initials: BH
authors.lastname: Tan
authors.forename: Torill
authors.initials: T
authors.lastname: Fladvad
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Braun
authors.forename: Antonio
authors.initials: A
authors.lastname: Vigano
authors.forename: Florian
authors.initials: F
authors.lastname: Strasser
authors.forename: D A Christopher
authors.initials: DA
authors.lastname: Deans
authors.forename: Richard J E
authors.initials: RJ
authors.lastname: Skipworth
authors.forename: Tora S
authors.initials: TS
authors.lastname: Solheim
authors.forename: Sambasivarao
authors.initials: S
authors.lastname: Damaraju
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Marks
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002100:Cachexia / Q000235:genetics*; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D019007:P-Selectin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D015431:Weight Loss / Q000235:genetics
chemical_list: D019007:P-Selectin; D002097:C-Reactive Protein