Role of MC1R variants in uveal melanoma

Abstract

Variants of the melanocortin-1 receptor (MC1R) gene have been linked to sun-sensitive skin types and hair colour, and may independently play a role in susceptibility to cutaneous melanoma. To assess the role of MC1R variants in uveal melanoma, we have analysed a cohort of 350 patients for the changes within the major region of the gene displaying sequence variation. Eight variants were detected -V60L, D84E, V92M, R151C, I155T, R160W, R163Q and D294H -63% of these patients being hetero-or homozygous for at least one variant. Standard melanoma risk factor data were available on 119 of the patients. MC1R variants were significantly associated with hair colour (P ¼ 0.03) but not skin or eye colour. The frequency of the variants detected in the 350 patients was comparable with those in the general population, and comparison of the cumulative tumour distribution by age at diagnosis in carriers and noncarriers provided no evidence that MC1R variants confer an increased risk of uveal melanoma. We interpret the data as indicating that MC1R variants do not appear to be major determinants of susceptibility to uveal melanoma.

Genetics of Primary Intraocular Tumors

“…One large study consisting of 350 UM patients and 133 controls detected eight MC1R variants (V60L, D84E, V92M, R151C, I155T, R160H, R163Q, and D294H), but found no significant difference in the frequencies of these variants between those with or without UM. 11 These results have been confirmed in other studies, which demonstrate that MC1R variants do not play a significant role in susceptibility to develop UM. 12,13 …”

Having Children, Social Characteristics, Smoking and the Risk of Uveal Melanoma: A Case-Control Study

“…There is no statistically significant association of the MC1R variants with ocular melanoma in both studies. 41,42 This could be the consequence of strata with small numbers of cases and controls with the respective genotypes in both analyses, and it does not necessarily rule out a possible association between MC1R variants and uveal melanoma risk.…”

Iris Colour and the Risk of Developing Uveal Melanoma

“…An important regulator of the eumelanin/pheomelanin ratio is melanocyte-stimulating hormone (MSH), which binds to its receptor (MC1R) on melanocytes. This receptor is only present on melanocytes, the brain, active monocytes, macrophages and dendritic cells [ 101 ]. The activation of MC1R on melanocytes leads to an increase of the intracellular levels of cAMP [ 102 ].…”