Table 2

Allelic frequencies of MC1R variants in patients with melanoma and in control subjects

Patients (n  =  216)Controls (n  =  210)Odds ratios (95% CI)p
n, number; NA, not applicable.
ORs are indicated with 95% confidence interval (CI).
Type 1 variants may not modify MC1R function, as these variants have not been previously associated with melanoma nor tested in functional assays (see statistical analyses in Material and Methods). These variants are pooled with the MC1R consensus sequence and considered as wild type in statistical analyses.
Type 2 variants have been shown to result in diminished MC1R function, and/or to be associated with fair pigmentation characteristics (RHC),29 and/or to be strongly associated with the risk of melanoma in previous studies.
*Fisher’s exact test.
MC1R variants unable to stimulate cAMP production as strongly as the wild type receptor in response to alpha melanocyte stimulating hormone (α-MSH).2–26
MC1R variants showing a decreased α-MSH binding affinity.25
§MC1R variants previously shown to be associated with melanoma risk.8,13,30
MC1R variants previously shown to be associated with the RHC phenotype.29
††MC1R variants predicted to be damaging (deducted from the Polyphen program).
MC1R consensus 46.3 (100)74.7 (157)
MC1R variants type 1
Val92Met5.6 (12)7.1 (15)
Arg163Gln4.6 (10)2.4 (5)
Thr95Met1.4 (3)0.9 (2)
Val180Ile0 (0)0.5 (1)
Total MC1R wt 57.9 (125)85.7 (180)1.0Reference
MC1R variants type 2
Arg151Cys†§††8.3 (18)1.9 (4)6.48 (2.14–19.61)0.0002
Arg160Trp†§7.9 (17)2.4 (5)4.73 (1.70–13.18)0.0013
Val60Leu†16.7 (36)6.2 (13)3.99 (2.03–7.82)<0.0001
Asp294His†‡§††3.7 (8)1.4 (3)3.84 (0.90–22.81)0.058*
Arg142His†‡††1.4 (3)0 (0)NA0.07*
Arg142Cys††0.5 (1)0 (0)NA0.41
Ile155Thr††0.9 (2)0.9 (2)1.44 (0.10–20.08)1.0
Ser83Pro††0.5 (1)0 (0)NA0.41
Asp84Glu§††1.4 (3)0.9 (2)2.16 (0.24–26.14)0.41*
Tyr298His††0.5 (1)0 (0)NA0.41
Val122Met‡0 (0)0.5 (1)NA1.0*
Ins 86‡‡0.5 (1)0 (0)NA0.41
Total variants type 242.1 (91)14.3 (30)4.37 (2.73–7.00)<0.0001