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Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia
Susanne Knoll1, Sabiene Zimmer, Anke Hinney
1Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Germany. susanneknoll@gmx.net
Background:
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.
Methods:
BMI (body mass index in kg/m2) 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.
Results:
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).
Conclusion:
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.
Insights
The melanocortin-4 receptor gene (MC4R) Val103Ile polymorphism does not increase cancer cachexia risk. Ile103 allele carriers may even be more resistant to cachexia in solid tumors.
Area of Science:
- Oncology
- Genetics
- Metabolism
Background:
- Cancer cachexia mechanisms are poorly understood.
- The melanocortin-4 receptor gene (MC4R) is implicated in cancer cachexia.
- MC4R mutations are linked to obesity; the Val103Ile polymorphism is negatively associated with obesity.
Purpose of the Study:
- To investigate if cancer patients with the Val103Ile polymorphism are more likely to develop cachexia or appetite loss.
- To assess the association between the MC4R Val103Ile polymorphism and cancer cachexia.
Main Methods:
- 509 cancer patients' BMI and appetite changes were assessed.
- Cachexia was defined as >=5% weight loss unrelated to other causes.
- Genotyping of the Val103Ile polymorphism was performed using PCR-RFLP.
Main Results:
- 21% of patients (107/509) met cachexia criteria.
- No association was found between Val103Ile polymorphism and cancer cachexia.
- A trend suggested heterozygotes for the 103Ile-allele developed cachexia less frequently (excluding early leukemia).
Conclusions:
- Cancer patients heterozygous for the 103Ile-allele are not more prone to cachexia.
- Ile103 carriers might exhibit increased resistance to cancer cachexia in solid tumors.
- Further research on the melanocortinergic system in solid tumor cachexia is recommended.
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