Importance of polymorphisms in NF-κB1 and NF-κBIα genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients

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Abstract
Importance of polymorphisms in NF-κB1 and NF-κBIα genes for melanoma risk, clinicopathological features and tumor progression is analyzed in Swedish melanoma patients. Functional polymorphisms of NF-κB1 and NF-κBIα genes were examined in 185 melanoma patients and 438 tumor-free individuals. Associations of the polymorphisms with melanoma risk, age and pigment phenotypes of the patients and clinicopathological tumor characteristics were analyzed. DNAs were isolated from mononuclear cells of venous blood. Polymorphisms of the genes were genotyped by a PCR-RFLP technique, and transcription level of NF-κBIα was examined by a quantitative real-time reverse transcription PCR. Both ATTG insertion polymorphism of NF-κB1 and A to G polymorphism of NF-κBIα genes were correlated with melanoma risk, especially, in a combination of ATTG 2 /ATTGT2 and GG. NF-κB1 ATTG2/ATTG2 and NF-κBIα GG genotypes were associated with male gender and age >65 years (at diagnosis). Patients with ATTG1/ATTG1 genotype had thinner tumors and lower Clark levels at diagnosis. Frequency of ATTG1/ATTG1 genotype was higher in patients with melanomas on intermittently sun-exposed pattern of the body and NF-κBIα GG was more frequent in the patients with melanomas at rarely exposed sites. There were no differences in the gene transcription level between patients with different NF-κBIα genotypes. NF-κB1 and NF-κBIα genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression.
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