Table 2.
Associations between two independent SNPs in the folate metabolic pathway genes and CMSS of patients in the MDACC dataset, the NHS/HPFS dataset and the MDACC and NHS/HPFS combined dataset
| MDACC (n=858) | NHS/HPFS (n=409) | MDACC + NHS/HPFS (n=1267) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | Frequency | Multivariate analysis1 | Frequency | Multivariate analysis2 | Frequency | Multivariate analysis3 | ||||||
| All | Death (%) | HR (95% CI) | P | All | Death (%) | HR (95% CI) | P | All | Death (%) | HR (95% CI) | P | |
| MTHFD1 rs1950902 G>A | ||||||||||||
| GG | 554 | 50 (9.03) | 1.00 | 275 | 24 (8.73) | 1.00 | 829 | 74 (8.93) | 1.00 | |||
| GA | 281 | 43 (15.30) | 1.92 (1.26–2.92) | 0.002 | 123 | 22 (17.89) | 2.27 (1.27–4.06) | 0.006 | 404 | 65 (16.09) | 1.97 (1.41–2.74) | 0.049 |
| AA | 23 | 2 (8.70) | 1.51 (0.36–6.25) | 0.573 | 11 | 2 (18.18) | 2.13 (0.50–9.10) | 0.308 | 34 | 4 (11.76) | 1.51 (0.55–4.15)) | 0.007 |
| Trend test | 0.005 | 0.007 | 0.0003 | |||||||||
| GA+AA | 304 | 45 (14.80) | 1.90 (1.25–2.87) | 0.003 | 134 | 24 (17.91) | 2.26 (1.28–3.99) | 0.005 | 438 | 69 (15.75) | 1.93 (1.39–2.68) | <.0001 |
| ALPL rs10917006 C>T | ||||||||||||
| CC | 751 | 77 (10.25) | 1.00 | 353 | 35 (9.92) | 1.00 | 1104 | 112 (10.14) | 1.00 | |||
| CT | 107 | 18 (16.82) | 1.83 (1.09–3.09) | 0.023 | 54 | 12 (22.22) | 2.34 (1.21–4.53) | 0.012 | 161 | 30 (18.63) | 1.92 (1.28–2.87) | <.0001 |
| TT | 0 | 0 (0.00) | - | - | 2 | 1 (50.00) | 5.44 (0.74–40.32) | 0.097 | 2 | 1 (50.00) | 4.94 (0.68–35.79) | 0.420 |
| Trend test | 0.023 | 0.004 | 0.0007 | |||||||||
| CT+TT | 107 | 18 (16.82) | 1.83 (1.09–3.09) | 0.023 | 56 | 13 (23.21) | 2.45 (1.29–4.65) | 0.006 | 163 | 31 (19.02) | 1.95 (1.31–2.91) | 0.001 |
| Combined number of risk genotypes4 | ||||||||||||
| 0 | 482 | 41 (8.51) | 1.00 | 236 | 17 (7.20) | 1.00 | 718 | 58 (8.08) | 1.00 | |||
| 1 | 341 | 45 (13.20) | 1.75 (1.13–2.71) | 0.012 | 156 | 25 (16.03) | 2.44 (1.31–4.52) | 0.005 | 497 | 70 (14.08) | 1.89 (1.33–2.68) | 0.0004 |
| 2 | 35 | 9 (25.71) | 4.32 (2.02–9.23) | 0.0002 | 17 | 6 (35.29) | 5.78 (2.25–14.84) | 0.0003 | 52 | 15 (28.85) | 4.18 (2.35–7.42) | <.0001 |
| Trend test | 0.0001 | <.0001 | <.0001 | |||||||||
| 0 | 482 | 41 (8.51) | 1.00 | 236 | 17 (7.20) | 1.00 | 718 | 58 (8.08) | 1.00 | |||
| 1–2 | 376 | 54 (14.36) | 1.95 (1.28–2.96) | 0.002 | 173 | 31 (17.92) | 2.73 (1.51–4.96) | 0.0009 | 549 | 85 (15.48) | 2.09 (1.49–2.92) | <.0001 |
Adjusted for age, sex, Breslow thickness, distant/regional metastasis, ulceration and mitotic rate in the MDACC dataset
Adjusted for age and sex in the NHS/HPFS dataset
Adjusted for age and sex in the MDACC and NHS/HpFS combined dataset
Risk genotypes include MTHFD1 rs1950902 GA+AA and ALPL rs10917006 CT+TT.
Abbreviations: SNP, single-nucleotide polymorphism; CMSS, cutaneous melanoma-specific survival; MDACC, The University of Texas MD Anderson Cancer Center; NHS/HPFS, the Nurses’ Health Study/Health Professionals Follow-up Study; HR, hazards ratio; CI, confidence interval; MTHFD1, methylenetetrahydrofolate dehydrogenase 1; ALPL, alkaline phosphatase.