Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Patients and Samples
2.3. Exome Analysis
Comparison of Allele and Genotype Frequencies between Melanoma and Control Samples
2.4. SNPs Genotyping
2.5. Statistical Analysis of Association
2.6. Disease-Free Survival (DFS) Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All Patients | Women | Men | |
---|---|---|---|
N | 1025 | 540 | 485 |
Age at diagnosis | Range 21–96 (median: 59) | Range 22–93 (median: 56) | Range 21–96 (median: 62) |
Disease evolution | |||
Disease free | 727 | 405 | 322 |
Metastasis | 298 | 135 | 163 |
Stage at diagnosis (AJCC 8th edition) | |||
In situ | 155 | 87 | 68 |
IA | 367 | 204 | 163 |
IB | 136 | 75 | 61 |
IIA | 77 | 41 | 36 |
IIB | 55 | 31 | 24 |
IIC | 59 | 26 | 33 |
IIIA | 31 | 13 | 18 |
IIIB | 22 | 10 | 12 |
IIIC | 57 | 20 | 37 |
IIID | 3 | 0 | 3 |
IV | 13 | 7 | 6 |
nd | 50 | 26 | 24 |
Melanoma subtypes | |||
SSM | 524 | 279 | 245 |
NM | 153 | 76 | 77 |
LM | 36 | 17 | 19 |
LMM | 52 | 29 | 23 |
ALM | 48 | 31 | 17 |
Others | 17 | 9 | 8 |
nd | 195 | 99 | 96 |
Breslow Thickness (mm) | |||
0 | 158 | 89 | 69 |
≤1 | 403 | 223 | 180 |
>1–2 | 176 | 91 | 85 |
>2–4 | 132 | 72 | 60 |
>4 | 116 | 46 | 70 |
nd | 40 | 19 | 21 |
Location | |||
Head/Neck | 158 | 70 | 88 |
Trunk | 424 | 165 | 259 |
Upper limb | 125 | 77 | 48 |
Lower limb | 230 | 173 | 57 |
Hands/foot | 56 | 39 | 17 |
Others | 19 | 11 | 8 |
All Patients | Women | Men | |
---|---|---|---|
N | 664 | 360 | 304 |
Age at diagnosis | Range 22–93 (median: 58) | Range 22–93 (median: 53) | Range 22–93 (median: 62) |
Disease evolution | |||
Disease free | 469 | 275 | 194 |
Metastasis | 195 | 85 | 110 |
Stage at diagnosis (AJCC 8th edition) | |||
In situ | 91 | 53 | 38 |
IA | 238 | 135 | 103 |
IB | 91 | 56 | 35 |
IIA | 61 | 33 | 28 |
IIB | 38 | 22 | 16 |
IIC | 42 | 19 | 23 |
IIIA | 17 | 7 | 10 |
IIIB | 11 | 5 | 6 |
IIIC | 46 | 16 | 30 |
IIID | 3 | 0 | 3 |
IV | 13 | 7 | 6 |
nd | 13 | 7 | 6 |
Melanoma subtypes | |||
SSM | 362 | 196 | 166 |
NM | 100 | 53 | 47 |
LM | 19 | 8 | 11 |
LMM | 21 | 13 | 8 |
ALM | 37 | 24 | 13 |
Others | 29 | 17 | 13 |
nd | 96 | 49 | 46 |
Breslow Thickness (mm) | |||
0 | 88 | 49 | 39 |
≤1 | 257 | 146 | 111 |
>1–2 | 116 | 64 | 52 |
>2–4 | 92 | 52 | 40 |
>4 | 85 | 33 | 52 |
nd | 26 | 16 | 10 |
Location | |||
Head/Neck | 86 | 35 | 51 |
Trunk | 265 | 105 | 160 |
Upper limb | 84 | 52 | 32 |
Lower limb | 165 | 124 | 41 |
Hands/foot | 42 | 31 | 11 |
Others | 12 | 8 | 4 |
nd | 10 | 5 | 5 |
Genotype N (%) | Chi2 Test | CATT Test | |||
---|---|---|---|---|---|
CC | CA | AA | p-Value | p-Value | |
All patients | |||||
Controls | 210 (27.2%) | 373 (48.2%) | 190 (24.6%) | 0.0044 | 0.0035 |
Patients | 221 (21.6%) | 494 (48.2%) | 310 (30.2%) | ||
Men | |||||
Controls | 65 (31%) | 105 (50%) | 40 (19%) | 0.0015 | 0.0030 |
Patients | 101 (20.8%) | 238 (49.1%) | 146 (30.1%) | ||
Women | |||||
Controls | 108 (24.7%) | 207 (47.2%) | 123 (28.1%) | 0.5915 | 0.2061 |
Patients | 120 (22.2%) | 256 (47.4%) | 164 (30.4%) |
Samples | Chi-Square Test (df = 2) (p-Value) | CATT Test: One-Sided (Theta = 1) (p-Value) | ||||
---|---|---|---|---|---|---|
ALL | WOMEN | MEN | ALL | WOMEN | MEN | |
All stages | 0.1526 | 0.7118 | 0.0308 | 0.0384 | 0.5968 | 0.0054 |
Stages I, II and III | 0.1188 | 0.4231 | 0.0287 | 0.0471 | 0.6761 | 0.0052 |
Stage II | 0.4493 | 0.8737 | 0.1503 | 0.1541 | 0.6162 | 0.0716 |
Genotype N (%) | Chi2 Test | CATT Test | |||
---|---|---|---|---|---|
CC | CA | AA | p-Value | p-Value | |
All stages (n = 304) | |||||
Disease-free | 45 (23.2%) | 91 (46.9%) | 58 (29.9%) | 0.0308 | 0.0054 |
Metastatic | 12 (10.9%) | 60 (54.55%) | 38 (34.55%) | ||
Stages I, II and III (n = 254) | |||||
Disease-free | 34 (21.9%) | 72 (46.5%) | 49 (31.6%) | 0.0287 | 0.0052 |
Metastatic | 9 (9.1%) | 53 (53.5%) | 37 (37.4%) | ||
Stage II (n = 67) | |||||
Disease-free | 6 (23.1%) | 12 (46.1%) | 8 (30.8%) | 0.1503 | 0.0716 |
Metastatic | 3 (7.3%) | 26 (63.4%) | 12 (29.3%) |
Samples | Univariate | Multivariate | |||
---|---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | ||
Men and women (n = 1025) | CC | 0.62 (0.42–0.93) | 0.0202 | 0.64 (0.41–1.01) | 0.0530 |
CA | 0.92 (0.69–1.22) | 0.5579 | 0.86 (0.63–1.18) | 0.3550 | |
Men and women, stages I, II, III (n = 807) | CC | 0.59 (0.38–0.89) | 0.0145 | 0.62 (0.39–0.99) | 0.0446 |
CA | 0.84 (0.63–1.14) | 0.2616 | 0.85 (0.62–1.18) | 0.3331 | |
Men (n = 485) | CC | 0.49 (0.27–0.89) | 0.0183 | 0.48 (0.25–0.94) | 0.0320 |
CA | 0.99 (0.68–1.44) | 0.9545 | 0.85 (0.55–1.30) | 0.4450 | |
Men, stages I, II, III (n = 387) | CC | 0.43 (0.23–0.82) | 0.0099 | 0.44 (0.21–0.89) | 0.0219 |
CA | 0.93 (0.63–1.38) | 0.7278 | 0.86 (0.56–1.32) | 0.4870 | |
Men, 5 years follow-up (n = 304) | CC | 0.46 (0.24–0.89) | 0.0200 | 0.4 (0.20–0.83) | 0.0139 |
CA | 0.95 (0.63–1.42) | 0.7940 | 0.68 (0.42–1.11) | 0.1218 | |
Men, 5 years follow-up, stages I, II, III (n = 254) | CC | 0.4 (0.19–0.83) | 0.0136 | 0.36 (0.16–0.79) | 0.0107 |
CA | 0.9 (0.59–1.37) | 0.6191 | 0.7 (0.43–1.13) | 0.1461 |
Samples | Univariate | Multivariate | ||
---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Men and women (n = 1025) | 0.66 (0.46–0.94) | 0.0222 | 0.7 (0.47–1.06) | 0.0904 |
Men and women, stages I, II, III (n = 807) | 0.65 (0.44–0.96) | 0.0308 | 0.68 (0.44–1.05) | 0.0789 |
Men (n = 485) | 0.50 (0.29–0.85) | 0.0110 | 0.54 (0.29–0.99) | 0.0459 |
Men, stages I, II, III (n = 387) | 0.45 (0.25–0.82) | 0.0086 | 0.48 (0.25–0.93) | 0.0290 |
Men, 5 years follow-up (n = 304) | 0.48 (0.26–0.87) | 0.0160 | 0.51 (0.26–0.99) | 0.0480 |
Men, 5 years follow-up, stages I, II, III (n = 254) | 0.43 (0.21–0.85) | 0.0147 | 0.45 (0.21–0.93) | 0.0318 |
CC (%) | CA (%) | AA (%) | N | |
---|---|---|---|---|
Men and women | 19.4 | 49.2 | 31.4 | 651 |
In situ | 24.2 | 46.1 | 29.7 | 91 |
Stage I | 20.7 | 49.5 | 29.8 | 329 |
Stage II | 16.3 | 51.1 | 32.6 | 141 |
Stage III | 11.7 | 48.0 | 40.3 | 77 |
Stage IV | 30.8 | 46.1 | 23.1 | 13 |
Men | 18.8 | 49.0 | 32.2 | 298 |
In situ | 26.3 | 50.0 | 23.7 | 38 |
Stage I | 22.5 | 45.6 | 31.9 | 138 |
Stage II | 13.4 | 56.7 | 29.9 | 67 |
Stage III | 6.1 | 49.0 | 44.9 | 49 |
Stage IV | 50.0 | 33.3 | 16.7 | 6 |
Women | 19.8 | 49.3 | 30.9 | 353 |
In situ | 22.6 | 43.4 | 34.0 | 53 |
Stage I | 19.4 | 52.3 | 28.3 | 191 |
Stage II | 18.9 | 46.0 | 35.1 | 74 |
Stage III | 21.4 | 46.4 | 32.2 | 28 |
Stage IV | 14.3 | 57.1 | 28.6 | 7 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
Variable | Coef | HR (95% CI) | p-Value | Coef | HR (95% CI) | p-Value |
Men and women | ||||||
Age | 0.0359 | 1.0365 (1.002–1.073) | 0.0404 | 0.0520 | 1.0534 (1.015–1.093) | 0.0061 |
Sex | 0.9262 | 2.5249 (0.828–7.704) | 0.1040 | - | - | - |
Breslow thickness | 0.0980 | 1.1029 (0.992–1.226) | 0.0693 | - | - | - |
Ulceration | 0.8022 | 2.2305 (0.842–5.907) | 0.1060 | - | - | - |
Melanoma subtypes | 0.0077 | 1.0078 (0.680–1.494) | 0.9690 | - | - | - |
rs1042602 genotype | −1.1387 | 0.3202 (0.127–0.809) | 0.0160 | −1.5605 | 0.2100 (0.079–0.555) | 0.0017 |
Men | ||||||
Age | 0.0340 | 1.0346 (0.997–1.074) | 0.0719 | - | - | - |
Breslow thickness | 0.0887 | 1.0928 (0.983–1.215) | 0.1 | - | - | - |
Ulceration | 1.1984 | 3.3148 (1.075–10.22) | 0.037 | 1.7475 | 5.7401 (1.594–20.657) | 0.0075 |
Melanoma subtypes | 0.1234 | 1.1313 (0.752–1.702) | 0.5540 | - | - | - |
rs1042602 genotype | −1.3253 | 0.2657 (0.090–0.787) | 0.0168 | −1.8709 | 0.154 (0.044- 0.539) | 0.0034 |
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Sevilla, A.; Sánchez-Diez, A.; Cobo, S.; Izagirre, N.; Martinez-Cadenas, C.; Martí, R.M.; Puértolas, T.; de Unamuno, B.; Bañuls, J.; Izu, R.; et al. Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis. Life 2022, 12, 2004. https://doi.org/10.3390/life12122004
Sevilla A, Sánchez-Diez A, Cobo S, Izagirre N, Martinez-Cadenas C, Martí RM, Puértolas T, de Unamuno B, Bañuls J, Izu R, et al. Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis. Life. 2022; 12(12):2004. https://doi.org/10.3390/life12122004
Chicago/Turabian StyleSevilla, Arrate, Ana Sánchez-Diez, Sofía Cobo, Neskuts Izagirre, Conrado Martinez-Cadenas, Rosa M. Martí, Teresa Puértolas, Blanca de Unamuno, José Bañuls, Rosa Izu, and et al. 2022. "Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis" Life 12, no. 12: 2004. https://doi.org/10.3390/life12122004