Torill Fladvad

Publications (2)10.33 Total impact

• Article: Is there a genetic cause of appetite loss?-an explorative study in 1,853 cancer patients.

  Tora S Solheim, Peter M Fayers, Torill Fladvad, Ben Tan, Frank Skorpen, Kenneth Fearon, Vickie E Baracos, Pål Klepstad, Florian Strasser, Stein Kaasa
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  ABSTRACT: Appetite loss has a major impact on cancer patients. It is exceedingly prevalent, is a prognostic indicator and is associated with inferior quality of life. Cachexia is a multi-factorial syndrome defined by a negative protein and energy balance, driven by a variable combination of reduced food intake and abnormal metabolism. Not all cancer patients that experience weight loss have appetite loss, and the pathophysiology between cachexia and appetite loss may thus be different. Knowledge of pathophysiology of appetite loss in cancer patients is still limited. The primary object of this study was to explore the association with 93 predefined candidate single-nucleotide polymorphisms (SNPs) and appetite loss in cancer patients to possibly generate new theories of the pathophysiology of the condition. A total of 1,853 cancer patients were phenotyped according to appetite loss and then genotyped. After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and appetite loss. The ten most significant SNPs in the co-dominant model had observed odds ratios varying from 0.72 to 1.28. This large exploratory study could not find any associations with loss of appetite and 93 SNPs with a potential to be involved in appetite loss in cancer patients. This does not however rule out genes putative role in the development of the symptom, but the observed odds ratios are close to one which makes it unlikely that any of the individual SNPs explored in the present study have great importance.
  Journal of cachexia, sarcopenia and muscle. 04/2012; 3(3):191-8.
• Article: P-selectin genotype is associated with the development of cancer cachexia.

  Benjamin H L Tan, Torill Fladvad, Theodore P Braun, Antonio Vigano, Florian Strasser, D A Christopher Deans, Richard J E Skipworth, Tora S Solheim, Sambasivarao Damaraju, James A Ross, Stein Kaasa, Daniel L Marks, Vickie E Baracos, Frank Skorpen, Kenneth C H Fearon
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  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.
  EMBO Molecular Medicine 04/2012; 4(6):462-71. · 10.33 Impact Factor