Melanocortin-1-receptor (MC1R) is one of the major genes that determine skin 
pigmentation. MC1R variants were suggested to be associated with red hair, fair 
skin, and an increased risk of melanoma. We performed a meta-analysis on the 
association between the 9 most studied MC1R variants (p.V60L, p.D84E, p.V92M, 
p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q and p.D294H) and melanoma and/or red 
hair, fair skin phenotype. Eleven studies on MC1R and melanoma, and 9 on MC1R 
and phenotype were included in the analysis. The 7 variants p.D84E, p.R142H, 
p.R151C, p.I155T, p.R160W, p. R163Q and p.D294H were significantly associated 
with melanoma development, with ORs (95%CI) ranging from 1.42 (1.09-1.85) for 
p.R163Q to 2.45 (1.32-4.55) for p.I155T. The MC1R variants p.R160W and p.D294H 
were associated both with red hair and fair skin, while p.D84E, p.R142H, and 
p.R151C were strongly associated with red hair only- ORs (95%CI) ranged from 
2.99 (1.51-5.91) for p.D84E to 8.10 (5.82-11.28) for p.R151C. No association 
with melanoma or phenotype was found for p.V60L and p.V92M variants. In 
conclusion this meta-analysis provided evidence that some MC1R variants are 
associated both with melanoma and phenotype, while other are only associated 
with melanoma development. These results suggest that MC1R variants could play a 
role in melanoma development both via pigmentary and non-pigmentary pathways.