LAUSR

Background: Breslow thickness is recognised as one of the most important prognostic tumour features in melanoma. In a recent pooled international study, the interferon regulatory factor-4 (IRF4) intron 4 rs12203592*T single nucleotide polymorphism (SNP) was associated with increased Breslow thickness [1]. Objective: Investigate whether this observation could be extended to include the analysis of IRF4 rs12203592 in nodular melanoma (NM), which is associated with a greater Breslow thickness at diagnosis compared with superficial spreading melanomas. Methods: Participants were recruited as part of the Brisbane Naevus Morphology Study. 432 melanoma case participants, with a personal history of one or more primary melanomas, were analysed along with 662 control individuals with no personal history of melanoma. All participants had genomic DNA extracted from 2ml of saliva collected using an Oragene-DNA selfcollection kit. Results: The IRF4 rs12203592*T allele had a frequency of 36.3% (n= 40) in the NM group compared to cutaneous melanoma group of 24.9% (n= 188), and 22.1% (n=293) in the control group (genotype P =0.015). The odds ratio for carrying the T allele in the NM group was 1.64 (95% confidence interval: 1.09–2.46) compared to the other melanoma patient group. We examined SNPs within an additional seven candidate genes associated with pigmentation, naevogenesis and melanoma (MITF, BNC2, MTAP, TYR, KITLG, HERC2/ OCA2 and PLA2G6) [2] and found no significant association with NM. Conclusions: Our findings report IRF4 as a potentially significant melanoma risk loci in NMs, which is consistent with Gibbs and colleagues findings indicating that the rs12203592* T SNP is associated with increased Breslow thickness in melanoma.