Is there a genetic cause for cancer cachexia? – a clinical validation study in 1797 patients

T.S. Solheim, Peter Fayers, T Fladvad, B Tan, F Skorpen, K. Fearon, V.E. Baracos, Pål Klepstad, F Strasser, S Kaasa

Research output: Contribution to journalArticle

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Abstract

BACKGROUND:
Cachexia has major impact on cancer patients' morbidity and mortality. Future development of cachexia treatment needs methods for early identification of patients at risk. The aim of the study was to validate nine single-nucleotide polymorphisms (SNPs) previously associated with cachexia, and to explore 182 other candidate SNPs with the potential to be involved in the pathophysiology.

METHOD:
A total of 1797 cancer patients, classified as either having severe cachexia, mild cachexia or no cachexia, were genotyped.

RESULTS:
After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and the cachexia groups. However, consistent with prior reports, two SNPs from the acylpeptide hydrolase (APEH) gene showed suggestive statistical significance (P=0.02; OR, 0.78).

CONCLUSION:
This study failed to detect any significant association between any of the SNPs analysed and cachexia; although two SNPs from the APEH gene had a trend towards significance. The APEH gene encodes the enzyme APEH, postulated to be important in the endpoint of the ubiquitin system and thus the breakdown of proteins into free amino acids. In cachexia, there is an extensive breakdown of muscle proteins and an increase in the production of acute phase proteins in the liver.
Original languageEnglish
Pages (from-to)1244-1251
Number of pages8
JournalBritish Journal of Cancer
Volume105
Issue number8
Early online date20 Sep 2011
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Cachexia
Validation Studies
Single Nucleotide Polymorphism
Neoplasms
Genes
Clinical Studies
Acute-Phase Proteins
Muscle Proteins
Ubiquitin
Morbidity
Amino Acids
Mortality
acylaminoacyl-peptidase
Liver

Keywords

  • cachexia
  • polymorphism
  • validation
  • genetic

Cite this

Is there a genetic cause for cancer cachexia? – a clinical validation study in 1797 patients. / Solheim, T.S.; Fayers, Peter; Fladvad, T; Tan, B; Skorpen, F; Fearon, K.; Baracos, V.E.; Klepstad, Pål; Strasser, F; Kaasa, S.

In: British Journal of Cancer, Vol. 105, No. 8, 10.2011, p. 1244-1251.

Research output: Contribution to journalArticle

Solheim, TS, Fayers, P, Fladvad, T, Tan, B, Skorpen, F, Fearon, K, Baracos, VE, Klepstad, P, Strasser, F & Kaasa, S 2011, 'Is there a genetic cause for cancer cachexia? – a clinical validation study in 1797 patients', British Journal of Cancer, vol. 105, no. 8, pp. 1244-1251. https://doi.org/10.1038/bjc.2011.323
Solheim, T.S. ; Fayers, Peter ; Fladvad, T ; Tan, B ; Skorpen, F ; Fearon, K. ; Baracos, V.E. ; Klepstad, Pål ; Strasser, F ; Kaasa, S. / Is there a genetic cause for cancer cachexia? – a clinical validation study in 1797 patients. In: British Journal of Cancer. 2011 ; Vol. 105, No. 8. pp. 1244-1251.
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AB - BACKGROUND:Cachexia has major impact on cancer patients' morbidity and mortality. Future development of cachexia treatment needs methods for early identification of patients at risk. The aim of the study was to validate nine single-nucleotide polymorphisms (SNPs) previously associated with cachexia, and to explore 182 other candidate SNPs with the potential to be involved in the pathophysiology.METHOD:A total of 1797 cancer patients, classified as either having severe cachexia, mild cachexia or no cachexia, were genotyped.RESULTS:After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and the cachexia groups. However, consistent with prior reports, two SNPs from the acylpeptide hydrolase (APEH) gene showed suggestive statistical significance (P=0.02; OR, 0.78).CONCLUSION:This study failed to detect any significant association between any of the SNPs analysed and cachexia; although two SNPs from the APEH gene had a trend towards significance. The APEH gene encodes the enzyme APEH, postulated to be important in the endpoint of the ubiquitin system and thus the breakdown of proteins into free amino acids. In cachexia, there is an extensive breakdown of muscle proteins and an increase in the production of acute phase proteins in the liver.

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