Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma.
Cutaneous malignant melanoma (CMM) is a potentially fatal malignancy in which exposure to UV light is the most important risk factor. Several lines of evidence suggest that CMM patients develop an immune response to their tumours, although, in most cases, anti-tumour immune responses are insufficient to abrogate tumour development. Polymorphism in genes regulating the immune response and cell growth may result in increased susceptibility to and/or poorer prognosis in certain individuals. In this study, we addressed whether single nucleotide polymorphisms (SNPs) associated with differential expression of selected pro- and anti-inflammatory cytokines and growth factors [interleukin (IL)-1beta-35 and -511, IL-2 -330, IL-4 -590, IL-6 -174, IL-8 -251, interferon (IFN)-gamma+874 and transforming growth factor (TGF)beta1 +915] or as markers of candidate cytokine genes (IL-12 +1188) are associated with susceptibility to or known prognostic indicators (e.g. initial tumour growth phase, Breslow thickness, mitotic count in vertical growth phase tumours, tumour regression) in CMM. One hundred and sixty-nine British caucasian CMM patients and 261 controls were included in the study and all SNPs were genotyped by ARMS-PCR. No SNP genotypes or alleles showed significant associations with CMM susceptibility and only the IL-1beta-511 TT genotype was associated with thinner invasive tumours at presentation, as assessed by Breslow thickness at the clinically significant cut-off point of 1.5 mm [occurring in 2/51 (3.9%) thicker vs. 14/78 (17.9%) thinner tumours (P = 0.03; relative risk = 0.29 (95% confidence interval 0.05-0.95)]. These findings suggest that - with the possible exception of IL-1beta- genetic variation associated with differential expression of the selected pro- and anti-inflammatory cytokines is unlikely to play a major role in susceptibility to and prognosis in CMM.
Howell
W M
WM
Department of Human Genetics, University of Southampton, UK. wmh1@soton.ac.uk
Turner
S J
SJ
Theaker
J M
JM
Bateman
A C
AC
D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008545:Melanoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma