Document Type
Article
Publication Date
12-21-2023
Publication Title
European Journal of Nutrition
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+.
PubMed ID
38129362
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Agudelo, María C.; Agudelo, Samuel; Lorincz, Attila; Ramírez, Arianis Tatiana; Castañeda, Kelly Melisa; Garcés-Palacio, Isabel; Zea, Arnold H.; Piyathilake, Chandrika; and Sanchez, Gloria Ines, "Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case–control study from the ASCUS-COL trial" (2023). School of Medicine Faculty Publications. 1843.
https://digitalscholar.lsuhsc.edu/som_facpubs/1843
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Biochemical Phenomena, Metabolism, and Nutrition Commons, Female Urogenital Diseases and Pregnancy Complications Commons, Heterocyclic Compounds Commons, Neoplasms Commons