Table 2.

Separate contributions of MC1R genotype, and self-reported and physician-measured traditional factors to risk prediction of melanoma, measured using the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI)

Risk factor1	AUC (95% CI)	Change in AUC from base model2	P3	Improvement in sensitivity4		Improvement in specificity4		Overall improvement in classification4
				NRI (95% CI)	P5	NRI (95% CI)	P5	NRI (95% CI)	P5
Base model with demographic6 factors only	0.67 (0.63, 0.72)
MC1R all variants7	0.73 (0.69, 0.77)	0.058	<0.001	0.12 (0.05, 0.19)	0.001	0.14 (0.06, 0.23)	<0.001	0.26 (0.15, 0.37)	<0.001
‘R’ variants only	0.72 (0.68, 0.75)	0.041	0.001	0.04 (−0.03, 0.11)	0.25	0.17 (0.09, 0.25)	<0.001	0.21 (0.10, 0.31)	<0.001
‘r’ variants only	0.68 (0.64, 0.72)	0.004	0.48	0.03 (−0.02, 0.07)	0.28	0.02 (−0.04, 0.08)	0.52	0.05 (−0.03, 0.12)	0.24
Self-reported risk factors
Nevi (none, few, some, many)	0.72 (0.68, 0.76)	0.048	0.001	0.15 (0.07, 0.23)	<0.001	0.09 (−0.00, 0.18)	0.06	0.24 (0.12, 0.36)	<0.001
Pigmentation score8	0.73 (0.69, 0.77)	0.053	<0.001	0.09 (0.03, 0.16)	0.004	0.12 (0.04, 0.20)	0.003	0.22 (0.11, 0.32)	<0.001
Sun & sunbed exposure9	0.69 (0.65, 0.73)	0.015	0.06	0.04 (−0.01, 0.09)	0.1	0.04 (−0.02, 0.10)	0.2	0.08 (0.00, 0.16)	0.04
Family history10	0.68 (0.64, 0.72)	0.006	0.4	0.01 (−0.02, 0.04)	0.6	0.03 (−0.01, 0.07)	0.2	0.04 (−0.01, 0.09)	0.2
Non-melanoma skin cancer11	0.70 (0.66, 0.74)	0.024	0.003	−0.03 (−0.06, 0.01)	0.2	0.09 (0.05, 0.13)	<0.001	0.06 (0.01, 0.12)	0.02
Physician-measured risk factors
Nevi 2+ mm	0.79 (0.75, 0.82)	0.111	<0.001	0.10 (0.03, 0.17)	0.008	0.29 (0.20, 0.38)	<0.001	0.39 (0.28, 0.51)	<0.001
Nevi 2–5 mm	0.78 (0.75, 0.82)	0.108	<0.001	0.10 (0.03, 0.17)	0.006	0.30 (0.21, 0.39)	<0.001	0.40 (0.29, 0.52)	<0.001
Nevi 5+ mm	0.76 (0.72, 0.79)	0.082	<0.001	−0.01 (−0.08, 0.06)	0.8	0.33 (0.25, 0.42)	<0.001	0.32 (0.21, 0.44)	<0.001
Nevi dysplastic	0.70 (0.66, 0.74)	0.027	0.01	−0.04 (−0.10, 0.01)	0.1	0.15 (0.09, 0.21)	<0.001	0.10 (0.02, 0.19)	0.02
Nevi raised	0.74 (0.70, 0.77)	0.061	<0.001	−0.04 (−0.11, 0.03)	0.2	0.29 (0.21, 0.36)	<0.001	0.24 (0.14, 0.35)	<0.001
Pigmentation score12	0.72 (0.68, 0.76)	0.047	0.001	0.11 (0.04, 0.17)	0.001	0.09 (0.01, 0.17)	0.03	0.20 (0.09, 0.30)	<0.001
Solar lentigines	0.74 (0.70, 0.78)	0.063	<0.001	0.09 (0.02, 0.16)	0.01	0.17 (0.08, 0.26)	<0.001	0.26 (0.15, 0.37)	<0.001

AUC Area under the receiver operating characteristic curve, NRI Net reclassification improvement.

¹ Each risk factor was separately added to the ‘base model’ to evaluate its influence on risk prediction.

² The change in the AUC between the base model and the model with the additional risk factor included.

³ Chi-square p-value for the difference in the AUC when compared to the base model.

⁴ Based on quartile cut-points. Improvement in sensitivity is calculated from reclassification of cases, improvement in specificity is calculated from reclassification of controls, and the overall improvement in classification combines the improvements in sensitivity and specificity.

⁵ The p-value, representing the statistical significance of the NRI, was calculated using the methods of Pencina et al.[29].

⁶ Demographic factors include age, sex, city of recruitment and European ancestry.

⁷MC1R is included as separate continuous variables for each of the six ‘R’ variants and one combined ‘r’ variant variable.

⁸ Self-reported ‘pigmentation score’ is a continuous variable derived from several self-reported variables including: ability to tan, propensity to sunburn, skin colour, eye colour, hair colour and childhood freckling.

⁹ ‘Sun & sunbed exposure’ includes total childhood sun exposure hours (quartiles), childhood blistering sunburns (none, ≤ 8, > 8), and lifetime number of sunbed sessions (0, 1–10, >10).

¹⁰ Confirmed family history of melanoma in a first degree relative (yes/no).

¹¹ A self-reported previous diagnosis of non-melanoma skin cancer.

¹² Objectively-measured ‘pigmentation score’ is a continuous variable derived from objectively-measured: hair colour, eye colour and skin reflectance (inner arm b* measure), and self-reported: ability to tan, propensity to sunburn and childhood freckling.