Oral Presentation ASDR Annual Scientific Meeting 2019

IRF4 rs12203592*T/T genotype is associated with nodular melanoma (#6)

Jenna E Rayner 1 , Erin K McMeniman 1 2 , David L Duffy 1 3 , Brian De’Ambrosis 2 , B. Mark Smithers 4 , Kasturee Jagirdar 1 , Katie J Lee 1 , H. Peter Soyer 1 2 , Richard A Sturm 1
  1. University of Queensland Diamantina Institute, Dermatology Research Centre Brisbane, QLD, AUS, Woolloongabba, QLD, Australia
  2. Princess Alexandra Hospital Dermatology Department , Brisbane, Queensland, Australia
  3. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  4. Queensland Melanoma Project, School of Medicine, The University of Queensland (UQ), Brisbane


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]. 



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.


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


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.


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.

  1. [1] Gibbs DC, Ward SV, Orlow I, Cadby G, Kanetsky PA, Luo L, et al. Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas. Br J Dermatol 2017; 177: e180–e182.
  2. [2] Rayner, J. , McMeniman, E. , Duffy, D. , De'Ambrosis, B. , Smithers, B. , Jagirdar, K. , Lee, K., Soyer, H. and Sturm, R. (2019), Melanoma Research. Accepted for publication as an 4.2.2019 "IRF4 rs12203592*T/T genotype is associated with nodular melanoma”. Original research letter in press, 20th March 2019
  • Are you an ECR (within 4 years of conferring of PhD)?: No
  • Are you an ECR (within 4 years of conferring of PhD)?: No