Journal
BRITISH JOURNAL OF CANCER
Volume 105, Issue 8, Pages 1244-1251Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.323
Keywords
cachexia; polymorphism; validation; genetic
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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. British Journal of Cancer (2011) 105, 1244-1251. doi:10.1038/bjc.2011.323 www.bjcancer.com Published online 20 September 2011 (C) 2011 Cancer Research UK
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