TABLE 1.
ALLELE FREQUENCIES FOR CDKN2A VARIANTS IDENTIFIED IN POPULATION-BASED ICELANDIC MELANOMA CASES AND CONTROLS
| Variant | Class | Allele Frequency
|
WMW2 P-value All Melanoma | OR for All Melanoma (95% CI) | WMW2 P-value invasive CMM | OR for invasive CMM (95% CI) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| All Melanoma (n~703) | Invasive CMM (n~470)1 | Melanoma In Situ (n~209) | Mucosal & Metastatic Melanoma (n~11) | Ocular Melanoma (n~14) | Controls (n~691) | ||||||
| CDKN2A p16 Variants | |||||||||||
| -981G>T | Promoter | 0.03 | 0.028 | 0.035 | 0 | 0.042 | 0.034 | 0.59 | 0.88 (0.57-1.36) | 0.46 | 0.83 (0.50-1.36) |
| -735G>A | Promoter | 0.018 | 0.019 | 0.018 | 0 | 0 | 0.027 | 0.15 | 0.67 (0.40-1.12) | 0.26 | 0.71 (0.40-1.27) |
| -493A>T | Promoter | 0.024 | 0.026 | 0.02 | 0.045 | 0 | 0.027 | 0.71 | 0.91 (0.56-1.48) | 1 | 0.98 (0.58-1.66) |
| c.-191G>A | 5′ UTR | 0.41 | 0.4 | 0.41 | 0.45 | 0.43 | 0.38 | 0.15 | 1.12 (0.96-1.31) | 0.24 | 1.11 (0.94-1.32) |
| c.-33G>C | 5′ UTR | 0.005 | 0.005 | 0.005 | 0 | 0 | 0.006 | 0.8 | 0.86 (0.27-2.74) | 1 | 0.93 (0.30-2.84) |
| c.-14C>T | 5′ UTR | 0.0014 | 0.0011 | 0.0024 | 0 | 0 | 0.0007 | 1 | -- | 1 | -- |
| IVS1+27A/C | Intron 1 | 0.0022 | 0.0032 | 0 | 0 | 0 | 0.0007 | 0.62 | 2.9 (0.2-154) | 0.31 | 4.4 (0.4-232) |
| IVS1+37G/C | Intron 1 | 0.0014 | 0.0011 | 0.0024 | 0 | 0 | 0 | 0.25 | -- | 0.4 | -- |
| IVS1-122G/C | Intron 1 | 0.0008 | 0 | 0.0025 | 0 | 0 | 0 | 0.5 | -- | -- | -- |
| A57V | Exon 2 | 0.003 | 0.0035 | 0.0026 | 0 | 0 | 0.003 | 1 | 1.01 (0.19-5.44) | 1 | 1.14 (0.17-6.75) |
| G89D | Exon 2 | 0.007 | 0.011 | 0 | 0 | 0 | 0.0008 | 0.011 | 9.2 (1.3 - 404) | 0.0015 | 13.8 (1.9-606) |
| A148T | Exon 2 | 0.025 | 0.025 | 0.025 | 0.05 | 0 | 0.027 | 0.72 | 0.91 (0.56-1.46) | 0.79 | 0.91 (0.53-1.55) |
| IVS2+83C/T | Intron 2 | 0.0015 | 0.0023 | 0 | 0 | 0 | 0.0015 | 1 | 1.02 (0.07-14.13) | 1 | 1.54 (0.11-21.22) |
| IVS2+227A/G | Intron 2 | 0.014 | 0.012 | 0.012 | 0.05 | 0.045 | 0.008 | 0.19 | 0.6 (0.25-1.34) | 0.38 | 1.53 (0.60-3.91) |
| Nt500C>G | 3′ UTR | 0.17 | 0.17 | 0.16 | 0.27 | 0.17 | 0.16 | 0.49 | 1.08 (0.88-1.32) | 0.56 | 1.07 (0.85-1.35) |
| Nt540C>T | 3′ UTR | 0.12 | 0.11 | 0.14 | 0.09 | 0.04 | 0.11 | 0.33 | 1.13 (0.89-1.43) | 0.78 | 1.04 (0.80-1.37) |
|
| |||||||||||
| p14/ARF Variants | |||||||||||
| TS -229A>T3 | Promoter | 0.0015 | 0.0023 | 0 | 0 | 0 | 0.0029 | 0.69 | 0.53 (0.05-3.68) | 1 | 0.79 (0.07-5.50) |
| TS -102C>T3 | Promoter | 0.018 | 0.022 | 0.011 | 0 | 0 | 0.022 | 0.48 | 0.80 (0.46-1.39) | 1 | 0.98 (0.54-1.76) |
| TS -89C>T3 | Promoter | 0.0025 | 0.0024 | 0.0028 | 0 | 0 | 0.003 | 1 | 0.83 (0.12-4.90) | 1 | 0.82 (0.07-5.75) |
| c.316+121T>C | Intron | 0.1 | 0.11 | 0.09 | 0 | 0.12 | 0.1 | 0.8 | 0.96 (0.74-1.24) | 0.89 | 1.02 (0.77-1.35) |
1
One patient had both invasive CMM and Ocular Melanoma. This case was included in the calculations for both melanomas.
2
Wilcoxon Mann-Whitney test
3
Locations relative to transcription start site, defined as first base in the sequence NM_058195