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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)

From: MC1Rgenotype as a predictor of early-onset melanoma, compared with self-reported and physician-measured traditional risk factors: an Australian case-control-family study

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

  1. AUC Area under the receiver operating characteristic curve, NRI Net reclassification improvement.
  2. 1 Each risk factor was separately added to the ‘base model’ to evaluate its influence on risk prediction.
  3. 2 The change in the AUC between the base model and the model with the additional risk factor included.
  4. 3 Chi-square p-value for the difference in the AUC when compared to the base model.
  5. 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.
  6. 5 The p-value, representing the statistical significance of the NRI, was calculated using the methods of Pencina et al.[29].
  7. 6 Demographic factors include age, sex, city of recruitment and European ancestry.
  8. 7 MC1R is included as separate continuous variables for each of the six ‘R’ variants and one combined ‘r’ variant variable.
  9. 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.
  10. 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).
  11. 10 Confirmed family history of melanoma in a first degree relative (yes/no).
  12. 11 A self-reported previous diagnosis of non-melanoma skin cancer.
  13. 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.
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BMC Cancer

ISSN: 1471-2407

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