Table 3.
Joint-analysis of the two identified independent SNPs in endosome-related pathway genes and CMSS of patients in the MDACC dataset, the NHS/HPFS dataset, and the MDACC and NHS/HPFS pooled dataset
| Genotype | MDACC (n = 858) | NHS/HPFS (n = 409) | MDACC+NHS/HPFS (n = 1267) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| Frequency | Multivariate analysis1 | Frequency | Multivariate analysis2 | Frequency | Multivariate analysis3 | |||||||
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| All | Death (%) | HR (95% CI) | P | All | Death (%) | HR (95% CI) | P | All | Death (%) | HR (95% CI) | P | |
| PIP5K1C rs11666894 A>C | ||||||||||||
| AA | 240 | 17 (7.08) | 1.00 | 98 | 8 (8.16) | 1.00 | 338 | 25 (7.40) | 1.00 | |||
| AC | 447 | 54 (12.08) | 1.70 (0.96-2.99) | 0.068 | 208 | 21 (10.10) | 1.28 (0.56-2.90) | 0.556 | 655 | 75 (11.45) | 1.59 (1.01-2.51) | 0.044 |
| CC | 171 | 24 (14.04) | 2.03 (1.05-3.90) | 0.035 | 103 | 19 (18.45) | 2.42 (1.06-5.54) | 0.037 | 274 | 43 (15.69) | 2.18 (1.33-3.57) | 0.002 |
| Trend test | 0.033 | 0.022 | 0.002 | |||||||||
| AC+CC | 618 | 78 (12.62) | 1.79 (1.03-3.08) | 0.040 | 311 | 40 (12.86) | 1.65 (0.77-3.54) | 0.197 | 929 | 118 (12.70) | 1.77 (1.15-2.72) | 0.010 |
| MVB12B rs12376285 C>T | ||||||||||||
| CC | 597 | 61 (10.22) | 1.00 | 265 | 21 (7.92) | 1.00 | 862 | 82 (9.51) | 1.00 | |||
| CT | 237 | 29 (12.24) | 1.48 (0.94-2.32) | 0.093 | 129 | 26 (20.16) | 2.60 (1.46-4.63) | 0.001 | 366 | 55 (15.03) | 1.55 (1.10-2.18) | 0.012 |
| TT | 24 | 5 (20.83) | 5.28 (2.00-13.95) | 0.001 | 15 | 1 (6.67) | 0.81 (0.11-6.00) | 0.833 | 39 | 6 (15.38) | 1.55 (0.67-3.56) | 0.302 |
| Trend test | 0.004 | 0.017 | 0.014 | |||||||||
| CT+TT | 261 | 34 (13.03) | 1.63 (1.06-2.51) | 0.027 | 144 | 27 (18.75) | 2.41 (1.36-4.26) | 0.003 | 405 | 61 (15.06) | 1.55 (1.11-2.16) | 0.010 |
| Number of risk genotypes4 | ||||||||||||
| 0 | 165 | 8 (4.85) | 1.00 | 60 | 4 (6.67) | 1.00 | 225 | 12 (5.33) | 1.00 | |||
| 1 | 507 | 62 (12.23) | 2.58 (1.16-5.72) | 0.020 | 243 | 21 (8.64) | 1.31 (0.45-3.84) | 0.618 | 750 | 83 (11.07) | 2.04 (1.11-3.74) | 0.021 |
| 2 | 186 | 25 (13.44) | 3.77 (1.61-8.87) | 0.002 | 106 | 23 (21.70) | 3.45 (1.19-10.03) | 0.023 | 292 | 48 (16.44) | 3.09 (1.64-5.82) | 5E-04 |
| Trend test | 0.002 | 0.001 | 2E-04 | |||||||||
| 0-1 | 672 | 70 (10.42) | 1.00 | 303 | 25 (8.25) | 1.00 | 975 | 95 (9.74) | 1.00 | |||
| 2 | 186 | 25 (13.44) | 1.69 (1.06-2.70) | 0.027 | 106 | 23 (21.70) | 2.76 (1.56-4.88) | 0.001 | 292 | 48 (16.44) | 1.71 (1.21-2.43) | 0.002 |
1
Adjusted for age, sex, Breslow thickness, distant/regional metastasis, ulceration and mitotic rate in the MDACC dataset;
2
Adjusted for age and sex in the NHS/HPFS dataset;
3
Adjusted for age and sex in the combined MDACC and NHS/HPFS dataset;
4
Risk genotypes include PIP5K1C rs11666894 AC+CC and MVB12B rs12376285 CT+TT.