Experimental oncology · 2025
ASSOCIATION OF INTRON 4 VNTR (4A/B) POLYMORPHISM OF THE ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE WITH THE INCIDENCE OF BREAST CANCER IN IRAQI WOMEN.
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M Hade Istikrar, A Ghadhban Zahraa, M Abd Ali Maryam, B Qaddoori Yasir
Аннотация
BACKGROUND: The VNTR 4a/b (rs61722009) polymorphism in intron 4 of the NOS3 gene is crucial for various biological processes and has been linked to cancer. Evidence suggests this polymorphism affects NOS3 gene expression and may promote tumor growth in the mammary gland.
AIM: This study aimed to investigate the association between NOS3 4a/b polymorphism and breast cancer (BC) susceptibility in Iraqi women, and to evaluate the potential correlation between these genetic variants and serum cancer antigen 15-3 (CA15-3) levels as a prognostic marker.
MATERIALS AND METHODS: The role of the 4a/b polymorphism was examined using PCR genotyping on dNA extracted from participants, including 50 women with BC and an equal number of controls. The level of CA15-3 was measured in the patients as well.
RESULTS: The homozygous wild-type b/b genotype may confer a protective effect against BC, with a significantly lower frequency in patients (8%) compared to controls (72%) (p < 0.01). Conversely, the heterozygous a/b and homozygous mutant a/ a genotypes were more frequent in patients (50% and 42%, respectively) than in controls (22% and 6%, respectively) (p < 0.01). Notably, the a/a genotype was significantly associated with increased BC risk (OR = 3.08, 95% CI: 1.19-5.47) and predominantly observed in the advanced pT2 stage. Additionally, the mean serum CA15-3 levels were significantly higher in patients with the a/a and a/b genotypes (15.66 U/mL and 22.91 U/mL, respectively) compared to those with the b/b genotype (6.37 U/mL) (p < 0.01).
CONCLUSION: The differences in genotype and allele frequencies between BC patients and healthy controls, along with the association of polymorphisms with CA15-3 levels, suggest that this genetic marker could serve as a valuable tool for risk assessment as well as prognosis in BC ptients. further investigations with larger and more diverse population samples are needed.
AIM: This study aimed to investigate the association between NOS3 4a/b polymorphism and breast cancer (BC) susceptibility in Iraqi women, and to evaluate the potential correlation between these genetic variants and serum cancer antigen 15-3 (CA15-3) levels as a prognostic marker.
MATERIALS AND METHODS: The role of the 4a/b polymorphism was examined using PCR genotyping on dNA extracted from participants, including 50 women with BC and an equal number of controls. The level of CA15-3 was measured in the patients as well.
RESULTS: The homozygous wild-type b/b genotype may confer a protective effect against BC, with a significantly lower frequency in patients (8%) compared to controls (72%) (p < 0.01). Conversely, the heterozygous a/b and homozygous mutant a/ a genotypes were more frequent in patients (50% and 42%, respectively) than in controls (22% and 6%, respectively) (p < 0.01). Notably, the a/a genotype was significantly associated with increased BC risk (OR = 3.08, 95% CI: 1.19-5.47) and predominantly observed in the advanced pT2 stage. Additionally, the mean serum CA15-3 levels were significantly higher in patients with the a/a and a/b genotypes (15.66 U/mL and 22.91 U/mL, respectively) compared to those with the b/b genotype (6.37 U/mL) (p < 0.01).
CONCLUSION: The differences in genotype and allele frequencies between BC patients and healthy controls, along with the association of polymorphisms with CA15-3 levels, suggest that this genetic marker could serve as a valuable tool for risk assessment as well as prognosis in BC ptients. further investigations with larger and more diverse population samples are needed.