Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case-control study from the ASCUS-COL trial

ABSTRACT: Purpose: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case-control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. Methods: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 SCC) and controls were age and follow-up time at diagnosis-matched women with histologically confirmed ≤ CIN1 (n = 155), selected from the 1122 hrHPV + women of this trial. The concentrations of serum folate were determined by the radioimmunoassay SimulTRAC-SNB-VitaminB12/Folate-RIAKit and the methylation levels by the S5 classifier. Stepwise logistic regression models were used to estimate the association between folate or methylation levels and CIN2+ or CIN3+. The joint effect of folate levels and methylation on the risk of CIN3+ was estimated using combinations of categorical stratifications. Results: Folate levels were significantly lower in women with CIN3+ than in other diagnostic groups (p = 0.019). The risk of CIN3+ was eight times higher (OR 8.9, 95% CI 3.4-24.9) in women with folate deficiency and high methylation levels than in women with normal folate and high methylation levels (OR 1.4, 95% CI 0.4-4.6). Conclusion: High methylation and deficient folate independently increased the risk of CIN3+ while deficient folate combined with high methylation was associated with a substantially elevated risk of CIN3+.

• Autores: Agudelo Fernández, María Cecilia; Agudelo Gamboa, Samuel; Ramírez Pineda, Arianis Tatiana; Castañeda Vanegas, Kelly Melisa; Garcés Palacio, Isabel Cristina; Sánchez Vásquez, Gloria; Lorincz, Attila; Zea, Arnold H.; Piyathilake, Chandrika
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2024
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/45268
• Acceso en línea: https://hdl.handle.net/10495/45268
• Palabra clave: Atypical Squamous Cells of the Cervix; Células Escamosas Atípicas del Cuello del Útero; Case-Control Studies; Estudios de Casos y Controles; DNA Methylation; Metilación de ADN; Folic Acid; Ácido Fólico; Folic Acid Deficiency; Deficiencia de Ácido Fólico; Uterine Cervical Dysplasia; Displasia del Cuello del Útero; https://id.nlm.nih.gov/mesh/D065309; https://id.nlm.nih.gov/mesh/D016022; https://id.nlm.nih.gov/mesh/D019175; https://id.nlm.nih.gov/mesh/D005492; https://id.nlm.nih.gov/mesh/D005494; https://id.nlm.nih.gov/mesh/D002578
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/