Table 4.
Associations of MC1R genotypes for grouped variants with melanoma, with and without adjustment for pigmentation and sun exposure, for case-unrelated-control and case-sibling-control comparisons
| MC1R variant | Case-unrelated-controla comparison | Case-sibling-control comparison | ||||||
|---|---|---|---|---|---|---|---|---|
|
|
||||||||
| Cases / controls | ORb (95% CI) | OR adj for pigmentationd (95% CI) | OR adj for pigmentation, nevi & sun exposuree (95% CI) | Cases / controls | ORc (95% CI) | OR adj for pigmentationd (95% CI) | OR adj for pigmentation, nevi & sun exposuree (95% CI) | |
| MC1R categories f | ||||||||
| wildtype only | 78/112 | 1.00 | 1.00 | 1.00 | 48/99 | 1.00 | 1.00 | 1.00 |
| 1 r and 0 R alleles | 108/105 | 1.60 (1.05–2.42) | 1.45 (0.95–2.22) | 1.39 (0.89–2.16) | 54/115 | 1.16 (0.62–2.16) | 1.14 (0.59–2.18) | 1.43 (0.72–2.84) |
| ≥2 r alleles and 0 R alleles | 49/28 | 2.68 (1.48–4.84) | 2.33 (1.27–4.25) | 2.26 (1.21–4.20) | 25/28 | 2.70 (0.99–7.40) | 2.83 (0.98–8.14) | 2.94 (0.95–9.04) |
| 1 R and 0 r alleles | 128/94 | 1.97 (1.30–2.99) | 1.69 (1.11–2.59) | 1.70 (1.09–2.65) | 82/117 | 2.17 (1.18–3.97) | 1.85 (1.00–3.45) | 1.87 (0.97–3.60) |
| 1 R and 1 r allele | 113/42 | 4.25 (2.60–6.95) | 3.13 (1.88–5.20) | 3.54 (2.08–6.05) | 64/104 | 2.21 (1.12–4.33) | 1.59 (0.78–3.24) | 1.67 (0.77–3.59) |
| 2 R alleles | 89/28 | 4.89 (2.84–8.43) | 2.42 (1.33–4.42) | 3.42 (1.81–6.47) | 55/55 | 4.52 (2.13–9.62) | 3.45 (1.59–7.47) | 4.16 (1.82–9.50) |
| Combined variants | ||||||||
| per r alleleg | 565/409 | 1.69 (1.33–2.13) | 1.53 (1.21–1.95) | 1.55 (1.20–1.99) | 328/518 | 1.25 (0.88–1.79) | 1.18 (0.81–1.71) | 1.23 (0.82–1.83) |
| per R alleleg | 565/409 | 2.23 (1.77–2.80) | 1.68 (1.30–2.16) | 1.93 (1.47–2.52) | 328/518 | 2.06 (1.47–2.88) | 1.74 (1.23–2.48) | 1.81 (1.24–2.65) |
| Per R or r allele | 565/409 | 1.96 (1.61–2.38) | 1.60 (1.30–1.96) | 1.71 (1.38–2.12) | 328/518 | 1.66 (1.25–2.20) | 1.47 (1.09–1.97) | 1.52 (1.10–2.10) |
Unrelated controls include population controls and spouse/friend controls.
Unconditional logistic regression, adjusted for age, sex, city of recruitment, and European ancestry. ORs were calculated as the risk associated with each additional variant allele carried.
Conditional logistic regression, matched on family and adjusted for age and sex. ORs were calculated as the risk associated with each additional variant allele carried.
Adjusted for the factors in footnote b, plus pigmentation score (continuous), which is a continuous variable derived from several variables including: usual skin response to sun exposure (ability to tan), propensity to sunburn, skin colour, eye colour, hair colour and childhood freckling.
Adjusted for the factors in footnote b, plus pigmentation score (continuous), lifetime total sun exposure (quartiles), nevus density (4 categories), lifetime blistering sunburns (none, ≤ 8, > 8), lifetime number of sunbed sessions (0, 1–10, >10).
The categories are mutually exclusive. Silent changes (i.e. changes that are synonymous or occur in non-coding regions) are counted as consensus alleles.
The models estimating the OR per `R' allele and per `r' allele were mutually adjusted in order to estimate their independent effects. r variants exclude silent changes (i.e. changes that are synonymous or occur in non-coding regions).