Involvement of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) levels in precancerous and cancerous cervical lesions
To assess the role of endothelial nitric oxide synthase (eNOS) in cervical cancer, we investigated the association between eNOS -786T/C and intron 4 VNTR 4b/a eNOS gene variations, plasma nitric oxide (NO) levels, cervical lesion occurrence, and disease progression. This study included 78 cervical lesions and 126 healthy controls. Genotyping was performed using polymerase chain reaction (PCR), and plasma NO levels were determined using the Griess reaction. We found that the -786C allele was significantly associated with cervical lesion risk (OR = 2.25; CI 95 % [1.15-4.41]; p = 0.025) and low-grade squamous intraepithelial lesion (L-SIL) risk (OR = 3.22; CI 95 % [1.09-9.686]; p = 0.042) but not with high-grade squamous intraepithelial lesion (H-SIL) and squamous cell carcinoma (SCC). Haplotype analysis showed that the C-4a haplotype was associated with a high risk of cervical lesion development (OR = 2.19, CI 95 % [1.149-4.2]; p = 0.025). Plasma NO levels differed depending on the eNOS variant genotype in cervical lesions and healthy controls. The presence of risk alleles (-786C and/or 4a) correlated with increased plasma NO levels in cervical lesions compared to healthy controls (p = 0.033 and p = 0.039, respectively). As well, the plasma NO levels were higher among cervical lesions than in healthy controls (p = 0.027), mainly among L-SIL (p = 0.004). Moreover, higher plasma NO levels were significantly associated with the presence of human papillomavirus (HPV) DNA among cervical lesions, as well as with a higher HPV circulating viral load. In conclusion, our findings highlight a significant association between eNOS genetic variants, plasma NO levels, and the occurrence and progression of cervical lesions.