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Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia

Abstract

At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. BMI (body mass index in kg/m{sup 2}) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Most of the patients suffered from  More>>
Authors:
Knoll, Susanne; Zimmer, Sabiene; [1]  Department of Hematology/Oncology/Immunology, University of Marburg (Germany)]; Hinney, Anke; [1]  Scherag, André; [2]  Neubauer, Andreas; [3]  Hebebrand, Johannes [1] 
  1. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen (Germany)
  2. Zentrum for clinical studies food (ZKSE) c/o Institute for Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen (Germany)
  3. Department of Hematology/Oncology/Immunology, University of Marburg (Germany)
Publication Date:
Mar 31, 2008
Product Type:
Journal Article
Resource Relation:
Journal Name: BMC cancer (Online); Journal Volume: 8; Other Information: PMCID: PMC2359760; PUBLISHER-ID: 1471-2407-8-85; PMID: 18377640; OAI: oai:pubmedcentral.nih.gov:2359760; Copyright (c) 2008 Knoll et al; licensee BioMed Central Ltd.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD; CARRIERS; GENES; HYBRIDIZATION; INDEXES; METABOLIC DISEASES; MUTATIONS; NEOPLASMS; PATIENTS; POLYMERASE CHAIN REACTION; RECEPTORS; SOLIDS; THERAPY; WEIGHT
OSTI ID:
22386342
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 1471-2407; TRN: GB15$2657091921
Availability:
Available from http://dx.doi.org/10.1186/1471-2407-8-85; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359760
Submitting Site:
INIS
Size:
page(s) 85
Announcement Date:
Oct 19, 2015

Citation Formats

Knoll, Susanne, Zimmer, Sabiene, Department of Hematology/Oncology/Immunology, University of Marburg (Germany)], Hinney, Anke, Scherag, André, Neubauer, Andreas, and Hebebrand, Johannes. Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia. United Kingdom: N. p., 2008. Web. doi:10.1186/1471-2407-8-85.
Knoll, Susanne, Zimmer, Sabiene, Department of Hematology/Oncology/Immunology, University of Marburg (Germany)], Hinney, Anke, Scherag, André, Neubauer, Andreas, & Hebebrand, Johannes. Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia. United Kingdom. doi:10.1186/1471-2407-8-85.
Knoll, Susanne, Zimmer, Sabiene, Department of Hematology/Oncology/Immunology, University of Marburg (Germany)], Hinney, Anke, Scherag, André, Neubauer, Andreas, and Hebebrand, Johannes. 2008. "Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia." United Kingdom. doi:10.1186/1471-2407-8-85. https://www.osti.gov/servlets/purl/10.1186/1471-2407-8-85.
@misc{etde_22386342,
title = {Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia}
author = {Knoll, Susanne, Zimmer, Sabiene, Department of Hematology/Oncology/Immunology, University of Marburg (Germany)], Hinney, Anke, Scherag, André, Neubauer, Andreas, and Hebebrand, Johannes}
abstractNote = {At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. BMI (body mass index in kg/m{sup 2}) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (± SD) was 59.0 ± 14.5 (males: 58.8 ± 14.0, females 59.2 ± 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of patients with solid tumors are warranted.}
doi = {10.1186/1471-2407-8-85}
journal = {BMC cancer (Online)}
volume = {8}
journal type = {AC}
place = {United Kingdom}
year = {2008}
month = {Mar}
}