Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population.
It has been hypothesized that polymorphisms expected to result in functional changes in cytokine genes may influence susceptibility to cancer, including malignant melanoma (MM). Here, we have screened 24 potentially functional polymorphisms in five cytokine genes by PCR-SBT and PCR-SSP methods in 122 MM cell lines derived from Caucasian patients. The polymorphic positions studied were: TNFA -1031, -863, -857, -851, -574, -376, -308, -238, +488; TGFB1 -988, -800, -509, +869, +915, +652, +673, +713, +788; IL10 -1082, -819, -592; IL6 -174; IFNG -333, +874. The frequencies of cytokine genotypes of melanoma tumours were compared with those published for healthy Caucasians. It was found that TNFA -238 GA, TGFB1 -509 CT, -800 GG, IFNG +874 AT, IL6 -174 GG, IL10 -1082 GA genotypes were significantly decreased, while TNFA -238 AA, -857 CC, TGFB1 -509 TT, IFNG +874 AA, IL6 -174 CC, IL10 -1082 AA, -819 TT, -592 AA genotypes were significantly increased, in MM. This suggests that genotypes provisionally associated with low expression of pro-inflammatory and immunomodulatory TNF-alpha, IFN-gamma and IL-6 and anti-inflammatory IL-10 and TGF-beta1 could be involved in the mechanisms of cancer progression and escape from immunosurveillance.
Nikolova
Penka N
PN
Central Laboratory of Clinical Immunology, University Hospital Alexandrovska, 1 Georgy Sofiisky Str., 1431 Sofia, Bulgaria. nikolova_p@yahoo.com
Pawelec
Graham P
GP
Mihailova
Snejina M
SM
Ivanova
Milena I
MI
Myhailova
Anastassia P
AP
Baltadjieva
Daniela N
DN
Marinova
Daniela I
DI
Ivanova
Svetlomira S
SS
Naumova
Elissaveta J
EJ
D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People
D016207:Cytokines; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma