Table 5.

Association of host phenotypes and melanocortin-1 receptor (MC1R) variants with melanoma risk in cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation carriers from all continents^*

Association of host phenotypes alone			Joint associations of host phenotypes and individual MC1R variants									Joint associations of host phenotypes and number of MC1R variants
Host phenotypes (272, 192)†	OR (95% CI)‡	P§	Host phenotypes and individual MC1R variants	MC1R variant
				V60L (112, 99)†		V92M (80, 97)†		R151C (115, 85)†		R160W (96, 84)†		Host phenotypes and No. of MC1R variants (272, 192)†
				OR (95% CI)‡	P§	OR (95% CI)‡	P§	OR (95% CI)‡	P§	OR (95% CI)‡	P§		OR (95% CI)‡	P§
Hair color	3.30 (1.98 to 5.52)	.0002	Hair color	2.87 (1.10 to 7.50)	.07	3.41 (1.19 to 9.77)	.04	3.26 (1.4 to 7.6)	.01	3.03 (1.34 to 6.87)	.02	Hair color	2.48 (1.46 to 4.20)	.004
			≥1 individual MC1R variant	2.89 (1.56 to 5.36)	.002	2.86 (1.38 to 5.95)	.008	3.69 (1.68 to 8.12)	.002	3.18 (1.5 to 6.74)	.01	1 MC1R variant	1.99 (1.20 to 3.29)	.01
												≥2 MC1R variants	4.74 (2.68 to 8.37)	1.6 × 10−5
Sunburn	2.10 (1.39 to 3.17)	.001	Sunburn	1.60 (.79 to 3.26)	.20	2.49 (1.05 to 5.89)	.04	2.03 (.86 to 4.82)	.10	2.49 (1.15 to 5.41)	.03	Sunburn	1.49 (.93 to 2.40)	.11
			≥1 individual MC1R variant	2.95 (1.55 to 5.62)	.003	2.54 (1.24 to 5.22)	.01	4.06 (1.87 to 8.85)	.001	3.67 (1.7 to 7.89)	.008	1 MC1R variant	1.99 (1.19 to 3.33)	.01
												≥2 MC1R variants	5.0 (2.76 to 9.07)	3.0 × 10−5
Nevi	3.05 (1.95 to 4.78)	1.3 × 10−5	Nevi	3.21 (1.49 to 6.91)	.005	2.82 (1.34 to 5.93)	.01	2.25 (1.2 to 4.22)	.02	2.14 (1.1 to 4.17)	.02	Nevi	3.0 (1.88 to 4.79)	2.6 × 10−5
			≥1 individual MC1R variant	2.88 (1.47 to 5.65)	.004	2.85 (1.3 to 6.25)	.01	4.88 (2.25 to 10.6)	.0003	4.28 (2.12 to 8.66)	.002	1 MC1R variant	2.05 (1.16 to 3.62)	.02
												≥2 MC1R variants	5.69 (3.08 to 10.50)	2.1 × 10−5
Hair color	2.34 (1.44 to 3.79)	.003	Hair color	3.05 (1.13 to 8.19)	.06	3.67 (1.28 to 10.56)	.04	3.27 (1.26 to 8.47)	.03	3.07 (1.25 to 7.53)	.03	Hair color	2.59 (1.44 to 4.64)	.006
Sunburn	2.07 (1.39 to 3.08)	.001	Sunburn	1.36 (.66 to 2.81)	.38	2.29 (.92 to 5.67)	.06	1.66 (.68 to 4.04)	.27	2.47 (1.12 to 5.43)	.03	Sunburn	1.38 (.86 to 2.21)	.19
Nevi	2.87 (1.91 to 4.31)	5.3 × 10−6	Nevi	3.25 (1.55 to 6.82)	.004	3.25 (1.61 to 6.56)	.003	2.29 (1.21 to 4.36)	.02	2.38 (1.18 to 4.81)	.01	Nevi	3.14 (2.00 to 4.91)	6.9 × 10−6
			≥1 individual MC1R variant	2.48 (1.26 to 4.88)	.01	2.44 (1.09 to 5.49)	.04	3.03 (1.4 to 6.58)	.007	2.66 (1.23 to 5.78)	.04	1 MC1R variant	1.98 (1.15 to 3.41)	.02
												≥2 MC1R variants	4.23 (2.27 to 7.87)	.0001

^*The associations of host phenotypes with melanoma risk were estimated by using the following dichotomous categories: hair color (blond or red vs dark or brown), propensity to sunburn (usually or always burns vs sometimes or never burns) and nevus count (some or many nevi vs none or few nevi). The association of each MC1R variable (individual MC1R variants, number of MC1R variants) with melanoma risk was estimated by using homozygosity for the MC1R consensus sequence as the reference category. CI = confidence interval; OR = odds ratio.

^†The number of affected (melanoma patients) and unaffected relatives contributing to a given analysis (host phenotypes alone, host phenotypes and individual MC1R variants, and host phenotypes and number of MC1R variants) are shown in parentheses; only the subjects who have all their host phenotypes known have been included in these analyses.

^‡The odds ratios and 95% confidence intervals were estimated by the generalized estimating equations method. The odds ratios were adjusted for age, sex, and geographic locales.

^§P values for the two-sided generalized score test of association between melanoma risk and any predictor variable (host phenotypes and/or MC1R variants).