Table 3.
Associations between three independent SNPs in the steroid hormone receptor-related genes and CMSS of patients in the MDACC study and Harvard study
|
Genotype |
MDACC
|
Harvard
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Frequency | Univariate analysis | Multivariate analysis1 | Frequency | Univariate analysis | Multivariate analysis2 | |||||||
|
|
|
|||||||||||
| All | Death (%) | HR (95%CI) | P | HR (95%CI) | P | All | Death (%) | HR (95%CI) | P | HR (95%CI) | P | |
| RORA rs782917 G>A | ||||||||||||
| GG | 542 | 50 (9.2) | 1.00 | 1.00 | 243 | 24 (9.9) | 1.00 | 1.00 | ||||
| GA | 276 | 37 (13.4) | 1.49(0.98–2.28) | 0.065 | 1.67 (1.08–2.59) | 0.021 | 143 | 18 (12.6) | 1.33(0.72–2.45) | 0.364 | 1.39 (0.75–2.58) | 0.292 |
| AA | 40 | 8 (20.0) | 2012(1.01–4.48) | 0.048 | 2.46 (1.15–5.28) | 0.021 | 23 | 6 (26.1) | 2.92(1.19–7.14) | 0.019 | 3.11 (1.25–7.72) | 0.015 |
| GA+AA | 316 | 45 (14.2) | 1.58(1.05–2.36) | 0.027 | 1.77(1.17–2.69) | 0.007 | 166 | 24 (14.46) | 1.54(0.87–2.71) | 0.138 | 1.61(0.91–2.85) | 0.104 |
| Trend | 0.015 | 1.61 (1.17–2.21) | 0.003 | 0.039 | 1.63 (1.06–2.52) | 0.027 | ||||||
| RORA rs17204952 C>T | ||||||||||||
| CC | 590 | 56 (9.5) | 1.00 | 1.00 | 286 | 27 (9.4) | 1.00 | 1.00 | ||||
| CT | 244 | 34 (13.9) | 1.51 (0.98–2.31) | 0.060 | 1.43 (0.92–2.22) | 0.113 | 111 | 19 (17.1) | 1.91 (1.06–3.44) | 0.030 | 1.91 (1.06–3.44) | 0.030 |
| TT | 24 | 5(20.8) | 2.166 (0.99–6.15) | 0.053 | 3.09 (1.22–7.85) | 0.018 | 12 | 2(16.67) | 1.71 (0.41–7.19) | 0.465 | 1.98 (0.47–8.37) | 0.352 |
| CT+TT | 268 | 39 (14.6) | 1.58 (1.05–2.38) | 0.027 | 1.54 (1.01–2.35) | 0.044 | 123 | 21 (17.1) | 1.89 (1.07–3.35) | 0.028 | 1.92 (1.09–3.40) | 0.025 |
| Trend | 0.014 | 1.56(1.09 –2.24) | 0.015 | 0.042 | 1.67(1.05 –2.66) | 0.030 | ||||||
| DNMT1 rs7253062 G>A | ||||||||||||
| GG | 297 | 27 (9.1) | 1.00 | 1.00 | 156 | 12 (7.7) | 1.00 | 1.00 | ||||
| GA | 430 | 50 (11.6) | 1.23(0.77–1.96) | 0.389 | 1.41 (0.86–2.30) | 0.173 | 185 | 22 (11.9) | 1.62(0.80–3.27) | 0.179 | 1.59 (0.79–3.21) | 0.198 |
| AA | 131 | 18 (13.7) | 1.53 (0.84–2.78) | 0.163 | 2.09 (1.13–3.87) | 0.018 | 68 | 14 (20.6) | 3.06 (1.41–6.62) | 0.005 | 2.78 (1.28–6.06) | 0.010 |
| GA+AA | 561 | 68 (12.1) | 1.30 (0.83–2.03) | 0.254 | 1.55(0.97–2.47) | 0.067 | 253 | 36 (14.2) | 1.98 (1.03–3.81) | 0.040 | 1.90(0.99–3.66) | 0.055 |
| Trend | 0.161 | 1.44(1.06–1.96) | 0.019 | 0.005 | 1.67(1.13–2.48) | 0.010 | ||||||
| Number of risk genotypes3 | ||||||||||||
| 0 | 127 | 7 (5.51) | 1.00 | 1.00 | 66 | 5 (7.58) | 1.00 | 1.00 | ||||
| 1 | 379 | 36 (9.50) | 1.71 (0.76–3.83) | 0.197 | 2.35 (0.97–5.68) | 0.057 | 175 | 12 (6.86) | 0.94 (0.33–2.66) | 0.900 | 0.89 (0.31–2.52) | 0.819 |
| 2 | 290 | 40 (13.79) | 2.42 (1.08–5.39) | 0.031 | 3.54 (1.48–8.49) | 0.005 | 137 | 24 (17.52) | 2.55 (0.97–6.68) | 0.060 | 2.55 (0.97–6.68) | 0.058 |
| 3 | 62 | 12 (19.35) | 3.89 (1.53–9.89) | 0.004 | 5.57 (2.02– 15.40) | 0.001 | 31 | 7 (22.58) | 3.51 (1.11–11.06) | 0.032 | 3.39 (1.07– 10.69) | 0.038 |
| Trend | 0.001 | 1.66 (1.28–2.15) | <0.001 | <0.001 | 1.79 (1.27–2.52) | <0.001 | ||||||
| 0-1 | 506 | 43 (8.5) | 1 | 1 | 241 | 17 (7.05) | 1.00 | 1.00 | ||||
| 2-3 | 352 | 52 (14.8) | 1.73 (1.16–2.59) | 0.008 | 1.97(1.29–3.00) | 0.002 | 168 | 30 (18.45) | 2.85 (1.58–5.15) | <0.001 | 2.94 (1.63–5.33) | <0.001 |
Abbreviations: SNP, single nucleotide polymorphisms; CMSS, cutaneous melanoma-specific survival; GWAS, genome-wide association study; MDACC, The University of Texas MD Anderson cancer center; HR, hazards ratio; CI, confidence interval;
1
Adjusted for age, sex, Breslow thickness, distant/regional metastasis, ulceration and mitotic rate in Cox models of SNPs and CMSS in MDACC study;
2
Adjusted for age and sex in Harvard study;
3
Risk genotypes include RORA rs782917 GA+AA, RORA rs17204952 CT+TT and DNMT1 rs7253062 GA+AA.