Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study
Abstract
:1. Introduction
2. Results
2.1. Distribution of TNF-α Genetic Polymorphisms between NB Cases and Control Group
2.2. Analysis of NB Patient Genotypes and Prognostic Factors
2.3. Relationship of TNF-α Serum Levels Between Cases of NB and Control Group
2.4. Association of Genotypes and Serum Levels
2.5. Survival Analysis
3. Discussion
4. Materials and Methods
4.1. Ethical Considerations
4.2. Determination of MYCN Gene Amplification
4.3. Analysis of TNF-α Genetic Polymorphisms
4.4. Measurement of TNF-α Serum Levels
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
SNP -238 G/A rs361525 n = 27 (%) | SNP -308 G/A rs1800629 n = 27 (%) | |||
---|---|---|---|---|
Variables | GG + GA | AA | GG | GA + AA |
INSS stage | ||||
1 | 3 (11.1) | 2 (7.4) | 5 (18.5) | ---- |
2b | 2 (7.4) | ---- | 1 (3.7) | 1 (3.7) |
3 | 7 (25.9) | ---- | 3 (11.1) | 4 (14.8) |
4 | 12 (44.4) | 1 (3.7) | 4 (14.8) | 9 (33.3) |
p value | 0.218 | 0.05 | ||
INRG | ||||
L1 | 3 (11.1) | 2 (7.4) | 3 (11.1) | 2 (7.4) |
L2 | 8 (29.6) | ---- | 5 (18.5) | 3 (11.1) |
M | 13 (48.1) | 1 (3.7) | 5 (18.5) | 9 (33.3) |
MS | ---- | --- | --- | |
p value | 0.146 | 0.51 | ||
Risk | ||||
Low | 3 (11.1) | 2 (7.4) | 4 (14.8) | 1 (3.7) |
Intermediate | 7 (25.9) | ---- | 5 (18.5) | 2 (7.4) |
High | 14 (51.9) | 1 (3.7) | 4 (14.8) | 11 (40.7) |
p value | 0.126 | 0.05 | ||
Differentiation | ||||
Undifferentiated | 2 (7.4) | ---- | ---- | 2 (7.4) |
Partially differentiated | 14 (51.9) | 2 (7.4) | 9 (33.3) | 7 (25.9) |
Differentiated | 4 (14.8) | 1 (3.7) | 3 (11.1) | 2 (7.4) |
Not specified | 4 (14.8) | ---- | 1 (3.7) | 3 (11.1) |
p value | 1 | 0.414 | ||
Histology (Shimada) | ||||
Favorable | 13 (48.1) | 2 (7.4) | 10 (37) | 5 (18.5) |
Unfavorable | 11 (40.7) | 1 (3.7) | 3 (11.1) | 9 (33.3) |
p value | 0.586 | 0.038 | ||
MYCN | ||||
Amplified | 1 (3.7) | ----- | ---- | 1 (3.7) |
Not amplified | 23 (85.2) | 3 (11.1) | 13 (48.1) | 13 (48.1) |
p value | 0.296 | 0.3 |
Low Serum TNF-α Levels | High Serum TNF-α Levels | Value p | OR (95% CI) | |
---|---|---|---|---|
TNF-α -308 G/A rs1800629 | ||||
GG | 12 (44.44) | 1 (3.7) | Ref | ---- |
GA | 4 (14.8) | 0 | --- | --- |
AA | 8 (29.6) | 2 (7.4) | 0.145 | 2.63 (0.71–9.70) |
GG + GA vs. AA | ----- | ----- | 0.119 | 7.27 (0.60–87.84) |
GA + AA vs. GG | ----- | ----- | 0.214 | 0.20 (0.017–2.47) |
TNF-α -238 G/A rs361525 | ||||
GG | 13 (48.14) | 0 | Ref | ---- |
GA | 8 (29.6) | 3 (11.1) | 0.118 | 3.87 (0.71–21.12) |
AA | 3 (11.1) | 0 | ----- | ------ |
GG + GA vs. AA | ----- | ---- | --- | NC |
GA + AA vs. GG | ----- | ---- | ---- | NC |
Model | HR (95% CI) | p Value |
---|---|---|
A | ||
TNF-α rs361525 (GG + GA vs. AA) | NC | NC |
Age (≥18 months vs. <18 months) | 1.16 (0.16–8.39) | 0.87 |
INSS stage (4 vs. 1, 2, 3) | 5.62 (0.51–61.6) | 0.15 |
MYCN (amplified vs. not amplified) | NC | NC |
B | ||
TNF-α rs1800629 (GG + GA vs. AA) | 2.08 (0.35–12.30) | 0.41 |
Age (≥18 months vs. <18 months) | 1.04 (0.14–7.64) | 0.96 |
INSS stage (4 vs. 1, 2, 3) | 5.16 (0.41–64.3) | 0.20 |
MYCN (amplified vs. not amplified) | NC | NC |
C | ||
Serum TNF-α levels (High vs. Low) | 4.95 (0.30–79.5) | 0.25 |
Age (≥18 months vs. <18 months) | 1.74 (0.20–15.12) | 0.61 |
INSS stage (4 vs. 1, 2, 3) | 4.91 (0.48–49.35) | 0.17 |
MYCN (amplified vs. not amplified) | NC | NC |
Appendix B
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Characteristics | Patients n = 27 (%) | Healthy Controls n = 38 (%) | |
---|---|---|---|
Age | <18 months | 16 (59.3) | 22 (57.9) |
18 months–5 years | 6 (22.2) | 9 (23.7) | |
>5 years | 5 (18.5) | 7 (18.4) | |
Sex | Male | 10 (37.03) | 14 (36.85) |
Female | 17 (62.97) | 24 (63.15) | |
INSS stage | 1 | 5 (18.5) | ----- |
2a | 0 (0) | ----- | |
2b | 2 (7.5) | ----- | |
3 | 7 (25.9) | ----- | |
4 | 13 (48.1) | ----- | |
4S | 0 (0) | ----- | |
INRG | L1 | 5 (18.5) | ----- |
L2 | 8 (29.6) | ----- | |
M | 14 (51.9) | ----- | |
MS | 0 (0) | ----- | |
Risk | Low | 5 (18.5) | ----- |
Intermediate | 7 (25.9) | ----- | |
High | 15 (55.6) | ----- | |
Primary Tumor Site | Adrenal | 8 (29.6) | ----- |
Retroperitoneal | 11 (40.7) | ----- | |
Paraspinal | 3 (11.1) | ----- | |
Abdomen/Pelvic | 1 (3.7) | ----- | |
Mediastinal | 4 (14.9) | ||
Differentiation | Undifferentiated | 2 (7.4) | ----- |
Partially differentiated | 16 (59.3) | ----- | |
Differentiated | 5 (18.5) | ----- | |
Not specified | 4 (14.8) | ----- | |
Histology (Shimada) | Favorable | 15 (55.6) | ----- |
Unfavorable | 12 (44.4) | ----- | |
MYCN | Amplified | 1 (3.7) | ----- |
Not amplified | 26 (96.3) | 38 (100) | |
Relapse | Yes | 7 (25.9) | |
Death | Yes | 6 (22.2) |
SNP | Controls (%) n = 38 | NB Patients (%) n = 27 | OR (95% CI) | p Value |
---|---|---|---|---|
TNF-α -238 G/A rs361525 | ||||
GG | 31 (81.6) | 13 (48.1) | Ref | |
GA | 7 (18.4) | 11 (40.7) | 4.52 (1.61–12.67) | 0.004 |
AA | 0 (0) | 3 (11.1) | ----- | --- |
GA + AA vs. GG | --- | --- | 0.20 (0.068–0.63) | 0.006 |
Allele G | 69 (90.79) | 37 (68.5) | ---- | ---- |
Allele A | 7 (9.21) | 17 (31.5) | ---- | ---- |
TNF-α -308 G/A rs1800629 | ||||
GG | 33 (86.8) | 13(48.2) | Ref | |
GA | 1 (2.6) | 4 (14.8) | ----- | |
AA | 4 (10.5) | 10 (37) | 2.89 (1.452–5.769) | 0.003 |
GG + GA vs. AA | ---- | ---- | 0.10 (0.030–0.393) | 0.001 |
GA + AA vs. GG | ---- | ---- | 5 (1.36–18.3) | 0.015 |
Allele G | 67 (88.15) | 30 (55.6) | --- | -- |
Allele A | 9 (11.84) | 24 (44.4) | ---- | ---- |
Variables | GG + GA | AA | OR * (95% CI) | p Value |
---|---|---|---|---|
Risk | ||||
Low | 3 (11.1) | 2 (7.4) | 1.5 (0.20–10.8) | 0.05 |
Intermediate/High | 21 (77.7) | 1 (3.7) | ||
INSS stage | ||||
stage 1, 2 | 5 (18.5) | 3 (11.1) | 0.043 (0.003–0.57) | 0.017 |
stage 3, 4 | 19 (70.3) | 1 (3.7) | ||
Histology (Shimada) | ||||
Favorable | 13 (48.1) | 2 (7.4) | 1.69 (0.134–21.26) | 0.68 |
Unfavorable | 11 (40.7) | 1 (3.7) | ||
MYCN | ||||
Amplified | 1 (3.7) | ---- | NC | NC |
Not amplified | 23 (85.2) | 3 (11.1) | ||
Death | ||||
Yes | 6 (22.2) | -- | NC | NC |
No | 18 (66.7) | 3 (11.1) |
Variables | GG | GA + AA | OR * (95% CI) | p Value |
---|---|---|---|---|
Risk | ||||
Low/Intermediate | 9 (33.3) | 3 (11.1) | 2.07 (0.39–10.8) | 0.04 |
High | 4 (14.8) | 11 (40.7) | ||
INSS stage | ||||
stage 1, 2 | 6 (22.2) | 1 (3.7) | 0.71 (0.07–6.53) | 0.76 |
stage 3,4 | 7 (25.9) | 13 (48.1) | ||
Histology (Shimada) | ||||
Favorable | 10 (37) | 5 (18.5) | 6 (1.10–32.5) | 0.03 |
Unfavorable | 3 (11.1) | 9 (33.3) | ||
MYCN | ||||
Amplified | --- | 1 (3.7) | NC | NC |
Not amplified | 13 (48.1) | 13 (48.1) | ||
Death | ||||
Yes | 1 (3.7) | 5 (18.5) | 0.15 (0.01–1.51) | 0.10 |
No | 12 (44.4) | 9 (33.3) |
TNF-α (pg/mL) | Controls n = 27 | NB Cases n = 27 |
---|---|---|
Range | 1.8–3 | 7.8–80.1 |
Mean | 2.474 | 11.851 |
Standard deviation (SD) | 0.358 | 14.86 |
p value | <0.001 | |
Low levels of TNF-α (≤20 pg/mL) | 27 (100) | 24 (88.9) |
High levels of TNF-α (≥21 pg/mL) | ------ | 3 (11.1) |
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Ramírez-Pacheco, A.; Moreno-Guerrero, S.S.; Rocha-Ramírez, L.M.; Hernández-Pliego, G.; Escobar-Sánchez, M.A.; Reyes-López, A.; Sienra-Monge, J.J.L.; Juárez-Villegas, L.E. Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study. Int. J. Mol. Sci. 2024, 25, 10590. https://doi.org/10.3390/ijms251910590
Ramírez-Pacheco A, Moreno-Guerrero SS, Rocha-Ramírez LM, Hernández-Pliego G, Escobar-Sánchez MA, Reyes-López A, Sienra-Monge JJL, Juárez-Villegas LE. Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study. International Journal of Molecular Sciences. 2024; 25(19):10590. https://doi.org/10.3390/ijms251910590
Chicago/Turabian StyleRamírez-Pacheco, Arturo, Silvia Selene Moreno-Guerrero, Luz María Rocha-Ramírez, Gabriela Hernández-Pliego, María Argelia Escobar-Sánchez, Alfonso Reyes-López, Juan José Luis Sienra-Monge, and Luis Enrique Juárez-Villegas. 2024. "Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study" International Journal of Molecular Sciences 25, no. 19: 10590. https://doi.org/10.3390/ijms251910590