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Divisive influence of interleukin-1 receptor antagonist polymorphisms in melanoma patients
P Niclas Broer1,2, Thiha Aung3, Paul I Heidekrueger2,3
1Section of Plastic and Reconstructive Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
Objective:
The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease.
Methods:
DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted via PCR amplification.
Results:
Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p > 0.05).
Conclusions:
Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation.
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