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

EMBO Molecular Medicine

Benjamin H. L. Tan⁴  Torill Fladvad²  Theodore P. Braun⁸  Antonio Vigano³  Florian Strasser⁵  D. A. Christopher Deans⁴  Richard J. E. Skipworth⁴  Tora S. Solheim¹  Sambasivarao Damaraju⁶  James A. Ross⁴  Stein Kaasa¹  Daniel L. Marks⁸  Vickie E. Baracos⁹  Frank Skorpen²  Kenneth C. H. Fearon⁷ 

[1] Faculty of Medicine, Clinical Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;Faculty of Medicine, Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;McGill Nutrition and Performance Laboratory, McGill University Health Centre, McGill University, Montreal, Canada;University of Edinburgh, Clinical and Surgical Sciences (Surgery), Royal Infirmary, Edinburgh, UK;Division of Oncology/Hematology, Department of Internal Medicine and Palliative Care Center, Oncological Palliative Medicine, Cantonal Hospital, St. Gallen, Switzerland;Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;E-mail address: 关键词: animal models;    cachexia;    inflammation;    polymorphisms;    P‐selectin;   

DOI  :  10.1002/emmm.201200231

来源: Wiley

【 摘 要 】

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.

See accompanying article http://dx.doi.org/10.1002/emmm.201200232

【 授权许可】

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