NOS3 Gene Polymorphisms (rs2070744 and rs1799983) and Differentiated Thyroid Cancer: Investigating Associations with Clinical Outcomes
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Study Design
- (a)
- Case group with documented DTC diagnoses ranging from 1978 to 2022.
- I.
- Inclusion criteria: patients over 18 years old with a confirmed pathological diagnosis of DTC.
- II.
- Exclusion criteria: incomplete information on the pathological examination, as well as missing information about the biochemical and structural responses following therapy.
- (b)
- Control group
- I.
- Inclusion criteria: subjects over 18 years old.
- II.
- Exclusion criteria: personal history of any thyroid disease, personal history of any malignant disease.
4.2. Data Collection
- (a)
- Indolent histological types: classic papillary carcinoma, papillary microcarcinoma, follicular variant of papillary microcarcinoma, follicular carcinoma, and Warthin-like variant.
- (b)
- Aggressive histological types: tall-cell variant, poorly differentiated component of follicular carcinoma, follicular carcinoma with insular carcinoma component, oncocytic carcinoma, and Hobnail variant.
4.3. Response to Therapy
4.4. Laboratory Methods
- rs1799983: T = wild-type allele; G = variant allele; TT = homozygous wild-type; GG = homozygous variant; GT = heterozygous variant.
- rs2070744: C = wild-type allele; T = variant allele; CC = homozygous wild-type; TT = homozygous variant; CT = heterozygous variant.
4.5. Statistical Analysis
4.6. Ethical Approval
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CASE GROUP | |
Number of subjects | 88 |
Sex distribution | F: 75 (85.2%) M: 13 (14.8%) |
Mean age at the last evaluation (years) | 55.46 ± 13.65 |
Median follow-up time (years) | 5 (4.0–7.6) |
Smoking status | NS: 63 (71.6%) S: 25 (28.4%) |
Type of surgical intervention | TT: 87 (98.9%) IL: 1 (1.1%) |
Histological type of DTC | Indolent: 76 (86.4%) Aggressive: 12 (13.6%) |
History of RAI administration | Yes: 68 (77.3%) No: 20 (22.7%) |
Loco-regional or distant metastases at diagnosis | Yes: 26 (29.5%) No: 62 (70.5%) |
Good biochemical control at last evaluation | Yes: 62 (70.5%) No: 26 (29.5%) |
Good structural control at last evaluation | Yes: 65 (73.9%) No: 23 (26.1%) |
Loco-regional or distant metastases after therapy | Yes: 6 (6.8%) No: 82 (93.2%) |
CONTROL GROUP | |
Number of subjects | 84 |
Sex distribution | F: 68 (81%) M: 16 (19%) |
Mean age | 54.41 ± 13.59 |
Polymorphism | Genotype | DTC Cases n (%) | Population Controls n (%) | p Value |
---|---|---|---|---|
rs2070744 | CC (homozygous wild type) | 16 (18.2%) | 13 (15.5%) | 0.387 |
CT (heterozygous variant) | 39 (44.3%) | 46 (54.7%) | ||
TT (homozygous variant) | 33 (37.6%) | 25 (29.8%) | ||
C (allele) | 71 (40.3%) | 72 (42.9%) | 0.716 | |
T (allele) | 105 (59.7%) | 96 (57.1%) | ||
rs1799983 | TT (homozygous wild type) | 8 (9.0%) | 8 (9.5%) | 0.329 |
GT (heterozygous variant) | 40 (45.5%) | 29 (34.5%) | ||
GG (homozygous variant) | 40 (45.5%) | 47 (56.0%) | ||
G (allele) | 120 (68.2%) | 123 (62.4%) | 0.292 | |
T (allele) | 56 (31.8%) | 74 (37.6%) |
Variable | OR | 95% CI | p Value |
---|---|---|---|
rs1799983 wild-type TT genotype | 0.191 | ||
rs1799983 heterozygous variant GT genotype | 1.870 | 0.953–3.668 | 0.069 |
rs1799983 homozygous variant GG genotype | 1.377 | 0.461–4.113 | 0.567 |
rs2070744 wild-type CC genotype | 0.224 | ||
rs2070744 heterozygous variant CT genotype | 0.701 | 0.298–1.650 | 0.416 |
rs2070744 homozygous variant TT genotype | 1.299 | 0.511–3.301 | 0.582 |
Polymorphism | Genotype | DTC Cases n (%) | p Value | Population Controls n (%) | p Value |
---|---|---|---|---|---|
rs2070744 | CC (homozygous wild type) | F: 13 (17.3%) M: 3 (23.1%) | 0.566 | F: 11 (16.2%) M: 2 (12.5%) | 0.787 |
CT (heterozygous variant) | F: 35 (46.7%) M: 4 (30.8%) | F: 36 (52.9%) M: 10 (62.5%) | |||
TT (homozygous variant) | F: 27 (36.0%) M: 6 (46.1%) | F: 21 (30.9%) M: 4 (25.0%) | |||
rs1799983 | TT (homozygous wild type) | F: 7 (9.3%) M: 1 (7.7%) | 0.982 | F: 6 (8.8%) M: 2 (12.5%) | 0.080 |
GT (heterozygous variant) | F: 34 (45.3%) M: 6 (46.1%) | F: 20 (29.4%) M: 9 (56.2%) | |||
GG (homozygous variant) | F: 34 (45.3%) M: 6 (46.1%) | F: 42 (61.8%) M: 5 (31.3%) |
NOS3 Gene Polymorphism | Clinicopathological Characteristic | p Value |
---|---|---|
rs1799983 | Male sex | 0.982 |
Smoking | 0.354 | |
Aggressive histological type | 0.944 | |
Incomplete biochemical control | 0.592 | |
Incomplete structural control | 0.204 | |
History of RAI therapy | 0.856 | |
Loco-regional/distance metastases | 0.725 | |
rs2070744 | Male sex | 0.566 |
Smoking | 0.958 | |
Aggressive histological type | 0.349 | |
Incomplete biochemical control | 0.907 | |
Incomplete structural control | 0.382 | |
History of RAI therapy | 0.436 | |
Loco-regional/distance metastases | 0.246 |
Genotype | Clinicopathological Characteristic | p Value |
---|---|---|
rs1799983 TT versus non-TT | Male sex | 0.849 |
Smoking | 0.295 | |
Aggressive histological type | 0.922 | |
History of RAI | 0.872 | |
Incomplete biochemical control | 0.768 | |
Incomplete structural control | 0.939 | |
Loco-regional/distant metastases | 0.422 | |
rs1799983 GG versus non-GG | Male sex | 0.956 |
Smoking | 0.517 | |
Aggressive histological type | 0.734 | |
History of RAI | 0.642 | |
Incomplete biochemical control | 0.394 | |
Incomplete structural control | 0.092 | |
Loco-regional/distant metastases | 0.817 | |
rs2070744 CC versus non-CC | Male sex | 0.620 |
Smoking | 0.781 | |
Aggressive histological type | 0.510 | |
History of RAI | 0.280 | |
Incomplete biochemical control | 0.660 | |
Incomplete structural control | 0.170 | |
Loco-regional/distant metastases | 0.232 | |
rs2070744 TT versus non-TT | Male sex | 0.485 |
Smoking | 0.855 | |
Aggressive histological type | 0.336 | |
History of RAI | 0.793 | |
Incomplete biochemical control | 0.904 | |
Incomplete structural control | 0.491 | |
Loco-regional/distant metastases | 0.126 |
Variable | OR | 95% CI | p Value |
---|---|---|---|
rs1799983 wild-type TT genotype | 0.907 | ||
rs1799983 heterozygous variant GT genotype | 1.342 | 0.359–5.018 | 0.662 |
rs1799983 homozygous variant GG genotype | 1.237 | 0.172–8.883 | 0.832 |
rs2070744 wild-type CC genotype | 0.989 | ||
rs2070744 heterozygous variant CT genotype | 1.050 | 0.213–5.182 | 0.952 |
rs2070744 homozygous variant TT genotype | 0.946 | 0.171–5.236 | 0.949 |
Incomplete structural control | 8.707 | 2.154–35.193 | 0.002 |
Male sex | 10.240 | 1.908–54.959 | 0.007 |
Smoking | 3.151 | 0.899–11.049 | 0.073 |
Aggressive histological type | 3.487 | 0.634–19.178 | 0.151 |
History of RAI | 0.130 | 0.028–0.595 | 0.009 |
Biological Data | Post-Therapeutic Evolution |
---|---|
Sex | Tumoral persistence |
Age | Tumoral recurrence |
Smoking status | Loco-regional or distant metastases |
Histological type of the tumor | |
Type of underwent treatment | |
Presence of loco-regional or distant metastases at diagnosis |
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Tiucă, R.A.; Pop, R.M.; Tiucă, O.M.; Bănescu, C.; Cârstea, A.C.; Preda, C.; Pașcanu, I.M. NOS3 Gene Polymorphisms (rs2070744 and rs1799983) and Differentiated Thyroid Cancer: Investigating Associations with Clinical Outcomes. Int. J. Mol. Sci. 2025, 26, 759. https://doi.org/10.3390/ijms26020759
Tiucă RA, Pop RM, Tiucă OM, Bănescu C, Cârstea AC, Preda C, Pașcanu IM. NOS3 Gene Polymorphisms (rs2070744 and rs1799983) and Differentiated Thyroid Cancer: Investigating Associations with Clinical Outcomes. International Journal of Molecular Sciences. 2025; 26(2):759. https://doi.org/10.3390/ijms26020759
Chicago/Turabian StyleTiucă, Robert Aurelian, Raluca Monica Pop, Oana Mirela Tiucă, Claudia Bănescu, Ana Claudia Cârstea, Cristina Preda, and Ionela Maria Pașcanu. 2025. "NOS3 Gene Polymorphisms (rs2070744 and rs1799983) and Differentiated Thyroid Cancer: Investigating Associations with Clinical Outcomes" International Journal of Molecular Sciences 26, no. 2: 759. https://doi.org/10.3390/ijms26020759
APA StyleTiucă, R. A., Pop, R. M., Tiucă, O. M., Bănescu, C., Cârstea, A. C., Preda, C., & Pașcanu, I. M. (2025). NOS3 Gene Polymorphisms (rs2070744 and rs1799983) and Differentiated Thyroid Cancer: Investigating Associations with Clinical Outcomes. International Journal of Molecular Sciences, 26(2), 759. https://doi.org/10.3390/ijms26020759