Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population
Abstract
:1. Introduction
2. Results
2.1. Polygenic Risk Score (PRS) Distribution Between Cases and Controls
2.2. Participant Characteristics According to the Quartile Distribution in Cases and Controls
2.3. Distribution of Genetic Variants Across PRS Quartiles
2.4. Associations Between Genetic Variations and Melanoma Risk
2.5. OCA2-HERC2 and MC1R Haplotype Frequencies
3. Discussion
4. Materials and Methods
4.1. Ethics Review Board Statement
4.2. Study Design and Population
4.3. DNA Preparation and Single-Nucleotide Polymorphism (SNP) Analysis
4.4. GWAS Databases and Variant Selection
4.5. Polygenic Risk Score Calculation
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PRS | Polygenic risk score |
GWAS | Genome-wide association study |
Q | Quartile |
SNP | Single-nucleotide polymorphisms |
AUC | Area under the curve |
OR | Odds ratio |
ROC | Receiver operating characteristic |
CI | Confidence intervals |
HWE | Hardy–Weinberg equilibrium |
HRM | High-resolution melting |
References
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PRS Quartile | Cases (85) | Controls (165) | Proportion | (95% CI) | p Value | |||
---|---|---|---|---|---|---|---|---|
Frequency | % | Frequency | % | |||||
Q1 | 29 | 34.1 | 34 | 20.6 | 0.46 | 0.336–0.590 | 0.6140 | |
Q2 | 15 | 17.6 | 47 | 28.5 | 0.242 | 0.146–0.370 | 0.0001 | *** |
Q3 | 14 | 16.5 | 48 | 29.1 | 0.226 | 0.133–0.353 | 0.0000 | **** |
Q4 | 27 | 31.8 | 36 | 21.8 | 0.429 | 0.307–0.559 | 0.3130 |
PRS Quartile 1 | PRS Quartile 2 | PRS Quartile 3 | PRS Quartile 4 | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cases (29) | Controls (34) | Cases (15) | Controls (47) | Cases (14) | Controls (48) | Cases (27) | Controls (36) | ||||||||||
N° | % | N° | % | N° | % | N° | % | N° | % | N° | % | N° | % | N° | % | ||
Sex | Female | 17 | 58.62 | 18 | 52.94 | 7 | 46.67 | 26 | 55.32 | 8 | 57.14 | 29 | 60.42 | 14 | 51.85 | 16 | 44.44 |
Men | 12 | 41.38 | 16 | 47.06 | 8 | 53.33 | 21 | 44.68 | 6 | 42.86 | 19 | 39.58 | 13 | 48.15 | 20 | 55.56 | |
Phototype | 2 | 4 | 13.79 | 5 | 14.71 | 2 | 13.33 | 8 | 17.02 | 5 | 35.71 | 12 | 25.00 | 5 | 18.52 | 6 | 16.67 |
3 | 21 | 72.41 | 26 | 76.47 | 11 | 73.33 | 31 | 65.96 | 7 | 50.00 | 35 | 72.92 | 20 | 74.07 | 25 | 69.44 | |
4 | 4 | 13.79 | 3 | 8.82 | 2 | 13.33 | 8 | 17.02 | 2 | 14.29 | 1 | 2.08 | 2 | 7.41 | 5 | 13.89 | |
Pathologic diagnostic | Acral lentiginous melanoma | 9 | 31.03 | - | - | 2 | 13.33 | - | - | 4 | 28.57 | - | - | 5 | 18.52 | - | - |
Lentigo maligna melanoma | 11 | 37.93 | - | - | 5 | 33.33 | - | - | 4 | 28.57 | - | - | 11 | 40.74 | - | - | |
Nodular melanoma | 3 | 10.34 | - | - | 2 | 13.33 | - | - | 3 | 21.43 | - | - | 5 | 18.52 | - | - | |
Superficial spreading melanoma | 6 | 20.69 | - | - | 6 | 40.00 | - | - | 3 | 21.43 | - | - | 5 | 18.52 | - | - | |
Clark grade | <1 mm | 1 | 3.45 | - | - | 1 | 6.67 | - | - | 0 | 0.00 | - | - | 0 | 0.00 | - | - |
2 mm | 1 | 3.45 | - | - | 2 | 13.33 | - | - | 1 | 7.14 | - | - | 2 | 7.41 | - | - | |
3 mm | 1 | 3.45 | - | - | 0 | 0.00 | - | - | 1 | 7.14 | - | - | 0 | 0.00 | - | - | |
>4 mm | 13 | 44.83 | - | - | 5 | 33.33 | - | - | 7 | 50.00 | - | - | 15 | 55.56 | - | - | |
Negative | 13 | 44.83 | - | - | 7 | 46.67 | - | - | 5 | 35.71 | - | - | 8 | 29.63 | - | - | |
Breslow scale | ≤1.0 mm | 4 | 13.79 | - | - | 1 | 6.67 | - | - | 2 | 14.29 | - | - | 4 | 14.81 | - | - |
>1.0–2.0 mm | 1 | 3.45 | - | - | 2 | 13.33 | - | - | 1 | 7.14 | - | - | 5 | 18.52 | - | - | |
>2.0–4.0 mm | 5 | 17.24 | - | - | 2 | 13.33 | - | - | 1 | 7.14 | - | - | 4 | 14.81 | - | - | |
>4.0 mm | 7 | 24.14 | - | - | 3 | 20.00 | - | - | 5 | 35.71 | - | - | 6 | 22.22 | - | - | |
Non reported | 12 | 41.38 | - | - | 7 | 46.67 | - | - | 5 | 35.71 | - | - | 8 | 29.63 | - | - | |
Location | Head and neck | 12 | 41.38 | - | - | 8 | 53.33 | - | - | 3 | 21.43 | - | - | 14 | 51.85 | - | - |
Trunk | 5 | 17.24 | - | - | 1 | 6.67 | - | - | 3 | 21.43 | - | - | 3 | 11.11 | - | - | |
Upper extremities | 2 | 6.90 | - | - | 0 | 0.00 | - | - | 1 | 7.14 | - | - | 2 | 7.41 | - | - | |
Lower extremities | 1 | 3.45 | - | - | 4 | 26.67 | - | - | 3 | 21.43 | - | - | 2 | 7.41 | - | - | |
Hands and Feets | 9 | 31.03 | - | - | 2 | 13.33 | - | - | 4 | 28.57 | - | - | 6 | 22.22 | - | - | |
Eye colors | Black or dark brown | 14 | 48.28 | 24 | 70.59 | 10 | 66.67 | 36 | 76.60 | 6 | 42.86 | 33 | 68.75 | 14 | 51.85 | 28 | 77.78 |
Blue | 1 | 3.45 | 2 | 5.88 | 1 | 6.67 | 2 | 4.26 | 0 | 0.00 | 3 | 6.25 | 0 | 0.00 | 0 | 0.00 | |
Light brown | 10 | 34.48 | 7 | 20.59 | 3 | 20.00 | 7 | 14.89 | 6 | 42.86 | 9 | 18.75 | 11 | 40.74 | 4 | 11.11 | |
Green | 4 | 13.79 | 1 | 2.94 | 1 | 6.67 | 1 | 2.13 | 2 | 14.29 | 3 | 6.25 | 2 | 7.41 | 4 | 11.11 | |
Hair colors | Black or dark brown | 21 | 72.41 | 28 | 82.35 | 12 | 80.00 | 39 | 82.98 | 7 | 50.00 | 34 | 70.83 | 15 | 55.56 | 34 | 94.44 |
Light brown | 8 | 27.59 | 5 | 14.71 | 3 | 20.00 | 8 | 17.02 | 7 | 50.00 | 13 | 27.08 | 11 | 40.74 | 2 | 5.56 | |
Red | 0 | 0.00 | 1 | 2.94 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 2.08 | 1 | 3.70 | 0 | 0.00 | |
Familiar cancer history | Yes | 17 | 58.62 | 16 | 47.06 | 7 | 46.67 | 19 | 40.43 | 7 | 50.00 | 27 | 56.25 | 17 | 62.96 | 16 | 44.44 |
No | 12 | 41.38 | 18 | 52.94 | 8 | 53.33 | 28 | 59.57 | 7 | 50.00 | 21 | 43.75 | 10 | 37.04 | 20 | 55.56 |
PRS Quartile | Cases (85) | Controls (165) | X2 | OR | (95% CI) | p Value | ||
---|---|---|---|---|---|---|---|---|
Sex (Female) | Q1 | 17 | 18 | 0.20 | 1.25 | 0.46–3.42 | 0.651 | |
Q2 | 7 | 26 | 0.34 | 0.71 | 0.22–2.26 | 0.558 | ||
Q3 | 8 | 29 | 0.05 | 0.87 | 0.26–2.91 | 0.826 | ||
Q4 | 14 | 16 | 0.33 | 1.35 | 0.49–3.66 | 0.560 | ||
Phototype (3) | Q1 | 21 | 26 | 0.13 | 0.80 | 0.25–2.51 | 0.710 | |
Q2 | 11 | 31 | 0.28 | 1.41 | 0.38–5.17 | 0.590 | ||
Q3 | 7 | 35 | 2.60 | 0.37 | 0.10–1.26 | 0.106 | ||
Q4 | 20 | 25 | 0.16 | 1.25 | 0.41–3.83 | 0.680 | ||
Eye Color | ||||||||
Black or dark brown | Q1 | 14 | 24 | 3.25 | 0.38 | 0.13–1.09 | 0.070 | |
Q2 | 10 | 36 | 0.58 | 0.61 | 0.17–2.17 | 0.440 | ||
Q3 | 6 | 33 | 3.11 | 0.34 | 0.100–1.15 | 0.070 | ||
Q4 | 14 | 28 | 4.66 | 0.30 | 0.10–0.91 | 0.031 | * | |
Light brown | Q1 | 10 | 7 | 1.53 | 2.03 | 0.65–6.28 | 0.210 | |
Q2 | 3 | 7 | 0.21 | 1.42 | 0.31–6.39 | 0.630 | ||
Q3 | 6 | 9 | 3.43 | 3.25 | 0.90–11.72 | 0.063 | ||
Q4 | 11 | 4 | 7.46 | 5.50 | 1.51–20.02 | 0.006 | ** | |
Hair colors | ||||||||
Black or dark brown | Q1 | 21 | 28 | 0.89 | 0.56 | 0.16–1.86 | 0.340 | |
Q2 | 12 | 39 | 0.06 | 0.82 | 0.18–3.59 | 0.790 | ||
Q3 | 7 | 34 | 2.10 | 0.41 | 0.12–1.39 | 0.140 | ||
Q4 | 15 | 34 | 13.50 | 0.07 | 0.01–0.36 | 0.000 | **** | |
Light brown | Q1 | 8 | 5 | 1.58 | 2.20 | 0.63–7.71 | 0.208 | |
Q2 | 3 | 8 | 0.06 | 1.21 | 0.27–5.33 | 0.790 | ||
Q3 | 7 | 13 | 2.60 | 2.69 | 0.79–9.17 | 0.106 | ||
Q4 | 11 | 2 | 11.66 | 11.68 | 2.31–59.03 | 0.001 | *** |
Model | Genotype Allele | Cases n = 85 (%) | Control n = 166 (%) | OR | (95% CI) | p Value |
---|---|---|---|---|---|---|
TYR (rs1042602—S192Y) | ||||||
Codominant | C/C | 46 (54.1%) | 74 (44.9%) | 1 | Reference | |
C/A | 35 (41.2%) | 66 (40%) | 1.08 | (0.58–2.01) | 0.096 | |
A/A | 4 (4.7%) | 25 (15.2%) | 3.44 | (1.01–11.70) | ||
Dominant | C/C | 46 (54.1%) | 74 (44.9%) | 1.32 | (0.73–2.38) | 0.36 |
C/A-A/A | 39 (45.9%) | 91 (55.1%) | ||||
Recessive | C/C-C/A | 81 (95.3%) | 140 (84.8%) | 3.32 | (1.01–10.94) | 0.032 |
A/A | 4 (4.7%) | 25 (15.2%) | ||||
Overdominant | C/C-A/A | 50 (58.8%) | 99 (60%) | 0.90 | (0.49–1.64) | 0.73 |
C/A | 35 (41.2%) | 66 (40%) | ||||
Log-additive | 1.46 | (0.92–2.31) | 0.1 | |||
TYRP1 (rs1408799) | ||||||
Codominant | T/T | 70 (82.3%) | 123 (74.5%) | 1 | Reference | |
T/C | 15 (17.6%) | 41 (24.9%) | 2.04 | (0.92–4.51) | 0.049 | |
C/C | 0 (0%) | 1 (0.6%) | NA | (NA) | ||
Dominant | T/T | 70 (82.3%) | 123 (74.5%) | 2.19 | (0.99–4.83) | 0.044 |
T/C-C/C | 15 (17.6%) | 42 (25.4%) | ||||
Recessive | T/T-T/C | 85 (100%) | 164 (99.4%) | NA | (0.00–NA) | - |
C/C | 0 (0%) | 1 (0.6%) | ||||
Overdominant | T/T-C/C | 70 (82.3%) | 124 (75.2%) | 1.97 | (0.90–4.33) | 0.08 |
T/C | 15 (17.6%) | 41 (24.9%) | ||||
Log-additive | 2.29 | (1.07–4.90) | 0.027 | |||
HERC2 (rs7170852—Intron56) | ||||||
Codominant | T/T | 34 (40%) | 89 (53.9%) | 1 | Reference | |
T/A | 50 (58.8%) | 42 (25.4%) | 0.28 | (0.14–0.55) | <0.0001 | |
A/A | 1 (1.2%) | 34 (20.6%) | 12.22 | (1.48–100.91) | ||
Dominant | T/T | 34 (40%) | 89 (53.9%) | 0.52 | (0.28–0.98) | 0.04 |
T/A-A/A | 51 (60%) | 76 (46.1%) | ||||
Recessive | T/T-T/A | 84 (98.8%) | 131 (79.4%) | 21.92 | (2.73–176.14) | <0.0001 |
A/A | 1 (1.2%) | 34 (20.6%) | ||||
Overdominant | T/T-A/A | 35 (41.2%) | 123 (74.5%) | 0.20 | (0.10–0.39) | <0.0001 |
T/A | 50 (58.8%) | 42 (25.4%) | ||||
Log-additive | 1.11 | (0.72–1.70) | 0.65 |
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Tovar-Parra, D.; Gutiérrez-Castañeda, L.D. Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population. Int. J. Mol. Sci. 2025, 26, 4674. https://doi.org/10.3390/ijms26104674
Tovar-Parra D, Gutiérrez-Castañeda LD. Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population. International Journal of Molecular Sciences. 2025; 26(10):4674. https://doi.org/10.3390/ijms26104674
Chicago/Turabian StyleTovar-Parra, David, and Luz Dary Gutiérrez-Castañeda. 2025. "Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population" International Journal of Molecular Sciences 26, no. 10: 4674. https://doi.org/10.3390/ijms26104674
APA StyleTovar-Parra, D., & Gutiérrez-Castañeda, L. D. (2025). Polygenic Risk Score Analysis of 37 SNPs Associated with Melanoma Risk in Colombian Population. International Journal of Molecular Sciences, 26(10), 4674. https://doi.org/10.3390/ijms26104674