title: Homocysteinemia is Associated with a Lower Degree of PBMC LINE-1 Methylation and a Higher Risk of CIN 2C in the U.S. Post-Folic Acid Fortification Era.
abstract: The primary aim of the study was to determine whether plasma concentrations of homocysteine (Hcy), a functional indicator of methyl donor nutrients, are associated with altered risk of higher grades of cervical intraepithelial neoplasia (CIN 2+) and the degree of methylation in long interspersed nucleotide elements (LINE-1s) of peripheral blood mononuclear cells, a potential biomarker of CIN 2+ in a population of women exposed to the United States folic acid fortification program. The secondary aim was to assess the determinants of plasma Hcy in the same population. The study included 457 women diagnosed with either CIN 2+ (cases, n = 132) or ≤ CIN 1 (non-cases, n = 325). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors of cervical cancer. Women with higher Hcy concentrations were at a greater risk of being diagnosed with CIN 2+ [odds ratio (OR) = 1.86, P = 0.005]. Higher plasma folate concentrations were a significant determinant of lower Hcy (OR = 0.40, P = 0.0002). Women with higher Hcy concentrations were more likely to have a lower degree of LINE-1 methylation (OR = 2.30, P = 0.0007). These results suggested that further improvement in folate status in this population may be beneficial for lowering Hcy and improving the degree of LINE-1 methylation.
authors.affiliation: a Department of Nutrition Sciences , University of Alabama at Birmingham , Birmingham , Alabama , USA.
authors.forename: Suguna
authors.initials: S
authors.lastname: Badiga
authors.affiliation: a Department of Nutrition Sciences , University of Alabama at Birmingham , Birmingham , Alabama , USA.
authors.forename: Nuzhat R
authors.initials: NR
authors.lastname: Siddiqui
authors.affiliation: b Department of Pediatrics , Division of Biostatistics and Epidemiology, The University of Cincinnati College of Medicine , Cincinnati , Ohio , USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Macaluso
authors.affiliation: c Biosciences Division, Center for Cancer and Metabolism, SRI International , Menlo Park , California , USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johanning
authors.affiliation: a Department of Nutrition Sciences , University of Alabama at Birmingham , Birmingham , Alabama , USA.
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood* / Q000235:genetics; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D016015:Logistic Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000235:genetics; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000209:etiology* / Q000235:genetics
chemical_list: D003278:Contraceptives, Oral, Hormonal; D006710:Homocysteine; D005492:Folic Acid