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The highly polymorphic melanocortin 1 receptor (MC1R) gene plays a crucial role in pigmentation. Variants of the gene have been implicated in risk of cutaneous squamous cell carcinoma (SCC) in the general population. In renal transplant (RT) recipients these cancers are more aggressive and very common. To evaluate the risk of SCC relative to MC1R and the pigmentation-associated genes ASIP, TYR, and TYRP1, a group of 217 RT recipients with and without SCC was genotyped. Associations with SCC risk were indicated in carriers of the red hair color associated MC1R variant p.Arg151Cys (OR = 1.99; 1.05-3.75), and in carriers of two of any of the MC1R variants disclosed (OR = 2.36; 1.08-5.15). These associations appeared independent of traditionally protective phenotypes, also supported by the stratifications from skin phototype and hair color. A tendency towards an increased SCC risk was observed for a specific ASIP haplotype (OR = 1.87; 0.91-3.83), while no such associations were observed for the TYR and TYRP1 variants. Thus, the risk of developing SCC in RT patients is modulated by MC1R variation irrespective of phenotypes considered to be protective. Heterozygous combinations of MC1R variants appear to be more relevant in assessing SCC risk than the effects of variants individually.

biomarkers in cancer.

Susceptibility to Cutaneous Squamous Cell Carcinoma in Renal Transplant Recipients Associates with Genes Regulating Melanogenesis Independent of their Role in Pigmentation