Interaction effects between blood folate and p16 gene expression in progression of cervical cancerization

Abstract

Objective To explore the interaction effects between blood folate and p16 gene expression in the progression of cervical cancerization. Methods The study participants included 58 patients with cervical inflammation (CI), 52 patients with cervical intraepithelial neoplasm Ⅰ (CIN Ⅰ), 60 patients with cervical intraepithelial neoplasm Ⅱ~Ⅲ (CIN Ⅱ~Ⅲ) and 76 patients with cervical squamous cell carcinoma (SCC), who were diagnosed by pathology. On the basis of collecting the demography information and cervical cancerization factors by structured questionnaire, blood folate levels were detected by microbiological assay, HPV16 infection status was determined by PCR, the expressions of p16 mRNA and protein were detected by real-time PCR and Western blot, respectively. Results The level of blood folate was (285.66±48.08) ng/ml in CI group, (268.70±46.01) ng/ml in CIN Ⅰ group, (251.22±32.20) ng/ml in CIN Ⅱ~Ⅲ group, (226.21±44.79) ng/ml in SCC group. Blood folate levels were decreased gradually with the deterioration of the cervical lesion (χ2trend=32.39, P<0.001), whereas levels of p16 mRNA expression (χ2trend=24.68,P<0.001) and protein expression (χ2trend=45.84, P<0.001) were increased. The levels of blood folate were negatively correlated with p16mRNA expression (r=-0.114, P<0.001) or protein expression (r=-0.192, P<0.001), and there was an additive interaction between blood folate deficiency and p16 mRNA or protein expression in CIN and SCC as well. Conclusions Both blood folate deficiency and high expression of p16 mRNA or protein could increase the risk of cervical cancerization, there may be a synergistic action between blood folate and p16 in the progression of cervical cancerization. Key words: Uterine cervical neoplasms; Blood folate; p16; Interaction