Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case–control study

• Published in: British journal of dermatology (1951) Vol. 178; no. 5; pp. 1119 - 1127
• Main Authors: Laino, A.M., Berry, E.G., Jagirdar, K., Lee, K.J., Duffy, D.L., Soyer, H.P., Sturm, R.A.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-05-2018
• Subjects: Data processing; Eye; Genotypes; Interferon regulatory factor 4; Iris; Melanoma; Risk factors; Saliva; Skin
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.16323

Summary
Background
Iris naevi and iris freckles have a frequency of 4% and 50% in the European population, respectively. They are associated with dysplastic naevi, but few studies have examined their link to cutaneous melanoma.
Objectives
To assess whether iris pigmented lesions are a predictive indicator for cutaneous melanoma.
Methods
This is a melanoma case–control study of 1254 European‐background Australians. Sun exposure and melanoma history, a saliva sample for DNA analysis and eye photographs taken with a digital camera were collected from 1117 participants. Iris images were assessed by up to four trained observers for the number of iris pigmented lesions. The data were analysed for correlations between iris pigmented lesions and melanoma history.
Results
Case participants over the age of 40 had similar numbers of iris pigmented lesions to age matched controls (mean 5·7 vs. 5·2, P = 0·02), but in younger case and control participants there was a greater difference (mean 3·96 vs. 2·19, P = 0·004). A logistic regression adjusted for age, sex, skin, hair and eye colour, skin freckling and naevus count found that the presence of three or more iris pigmented lesions increases the melanoma risk 1·45‐fold [95% confidence interval (CI) 1·07–1·95]. HERC2/OCA2 rs12913832 and IRF4 rs12203592 influenced both eye colour and the number of iris pigmented lesions. On the HERC2/OCA2 A/A and A/G genotype background there was an increasing proportion of blue eye colour when carrying the IRF4 T allele (P = 3 × 10−4) and a higher number of iris pigmented lesions with the IRF4 T/T homozygote (P = 3 × 10−9).
Conclusions
Iris pigmented lesion count provides additional predictive information for melanoma risk above that from conventional risk factors.
What's already known about this topic?
Clinicians should be aware of groups at high risk for melanoma to facilitate early detection; melanoma survival rates remain highest when the melanoma is identified at a localized stage and drop steeply if the melanoma has spread regionally.
Well‐established melanoma risk factors include phenotypic characteristics such as skin type and numbers of melanocytic naevi on the skin.
What does this study add?
We found a 45% increased risk of cutaneous melanoma associated with the presence of three or more iris pigmented lesions.
This association was particularly strong in study participants aged 40 years or under.
Iris pigmented lesion count therefore provides additional predictive information for melanoma risk stratification over and above currently used phenotypic factors such as skin type, hair and eye colour and naevus count.
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