Levels of Folate and Vitamin B12, and Genetic Polymorphisms Involved in One-Carbon Metabolism May Increase the Risk of Cervical Cytological Abnormalities

Abstract

To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42–8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46–18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

Acknowledgments

To Laboratório de Análises Clínicas (LAPAC) for cytological analysis and for infrastructure for micronutrients analysis.

Authors’ Contribution

SILVA, NNT; SANTOS, ACS; PEIXODO DO VALE, DBA; CARNEIRO, CM; and LIMA, AA analyzed and interpreted the patient data regarding the cytological analyses, HPV infection, and genetic polymorphisms. BRITO, MFDS assisted in selection of participants, and collection of cervical samples. All authors read and approved the final manuscript.

Conflict of Interest

There is no conflict of interest.

Consent to Participate

Written informed consent have been obtained from all participants (CAAE 57187316.7.0000.5150, and CAAE 88479718.0.0000.5150).

Ethics Approval

Research Ethics Committee of the Federal University of Ouro Preto approved this study (CAAE 57187316.7.0000.5150, and CAAE 88479718.0.0000.5150).

Additional information

Funding

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG (APQ02807-10).