Publication Date:
2015-05-09
Description:
Actinic keratosis (AK) is a pre-malignant skin disease, highly prevalent in elderly Europeans. This study investigates genetic susceptibility to AK with a genome-wide association study (GWAS). A full body skin examination was performed in 3194 elderly individuals from the Rotterdam Study (RS) of exclusive north-western European origin (aged 51–99 years, 45% male). Physicians graded the number of AK into four severity levels: none (76%), 1–3 (14%), 4–9 (6%) and ≥10 (5%), and skin color was quantified using a spectrophotometer on sun-unexposed skin. A GWAS for AK severity was conducted, where promising signals at IRF4 and MC1R ( P 〈 4.2 x 10 –7 ) were successfully replicated in an additional cohort of 623 RS individuals ( IRF4 , rs12203592, P combined = 6.5 x 10 –13 and MC1R , rs139810560, P combined = 4.1 x 10 –9 ). Further, in an analysis of ten additional well-known human pigmentation genes, TYR also showed significant association with AK (rs1393350, P = 5.3 x 10 –4 ) after correction for multiple testing. Interestingly, the strength and significance of above-mentioned associations retained largely the same level after skin color adjustment. Overall, our data strongly suggest that IRF4 , MC1R and TYR genes likely have pleiotropic effects, a combination of pigmentation and oncogenic functions, resulting in an increased risk of AK.
Print ISSN:
0964-6906
Electronic ISSN:
1460-2083
Topics:
Biology
,
Medicine
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