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Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN.

Abstract

We previously reported that a higher degree of methylation of CpG sites in the promoter (positions 31, 37, 43, 52, and 58) and enhancer site 7862 of human papillomavirus (HPV) 16 was associated with a lower likelihood of being diagnosed with HPV 16-associated CIN 2+. The purpose of this study was to replicate our previous findings and, in addition, to evaluate the influence of plasma concentrations of folate and vitamin B12 on the degree of HPV 16 methylation (HPV 16m). The study included 315 HPV 16-positive women diagnosed with either CIN 2+ or ≤CIN 1. Pyrosequencing technology was used to quantify the degree of HPV 16m. We reproduced the previously reported inverse association between HPV 16m and risk of being diagnosed with CIN 2+. In addition, we observed that women with higher plasma folate and HPV 16m or those with higher plasma vitamin B12 and HPV 16m were 75% (P < 0.01) and 60% (P = 0.02) less likely to be diagnosed with CIN 2+, respectively. With a tertile increase in the plasma folate or vitamin B12, there was a 50% (P = 0.03) and 40% (P = 0.07) increase in the odds of having a higher degree of HPV 16m, respectively. This study provides initial evidence that methyl donor micronutrients, folate and vitamin B12, may play an important role in maintaining a desirably high degree of methylation at specific CpG sites in the HPV E6 promoter and enhancer that are associated with the likelihood of being diagnosed with CIN 2+.

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  • Authors+Show Affiliations

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    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama. piyathic@uab.edu.

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    University of Cincinnati College of Medicine, Cincinnati, Ohio.

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    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama.

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    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama.

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    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama.

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    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.

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    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

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    University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama.

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    Department of Obstetrics & Gynecology, University of Alabama at Birmingham, Birmingham, Alabama.

    Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas and SRI International, Menlo Park, CA.

    Source

    MeSH

    Adult
    Biopsy
    Cervical Intraepithelial Neoplasia
    CpG Islands
    DNA Methylation
    DNA, Viral
    Enhancer Elements, Genetic
    Female
    Folic Acid
    Genotype
    Human papillomavirus 16
    Humans
    Male
    Micronutrients
    Middle Aged
    Oncogene Proteins, Viral
    Papillomavirus Infections
    Promoter Regions, Genetic
    Repressor Proteins
    Risk Factors
    Sequence Analysis, DNA
    Vitamin B 12
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    25145486

    Citation

    Piyathilake, Chandrika J., et al. "Folate and Vitamin B12 May Play a Critical Role in Lowering the HPV 16 Methylation-associated Risk of Developing Higher Grades of CIN." Cancer Prevention Research (Philadelphia, Pa.), vol. 7, no. 11, 2014, pp. 1128-37.
    Piyathilake CJ, Macaluso M, Chambers MM, et al. Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN. Cancer Prev Res (Phila). 2014;7(11):1128-37.
    Piyathilake, C. J., Macaluso, M., Chambers, M. M., Badiga, S., Siddiqui, N. R., Bell, W. C., ... Johanning, G. L. (2014). Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN. Cancer Prevention Research (Philadelphia, Pa.), 7(11), pp. 1128-37. doi:10.1158/1940-6207.CAPR-14-0143.
    Piyathilake CJ, et al. Folate and Vitamin B12 May Play a Critical Role in Lowering the HPV 16 Methylation-associated Risk of Developing Higher Grades of CIN. Cancer Prev Res (Phila). 2014;7(11):1128-37. PubMed PMID: 25145486.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN. AU - Piyathilake,Chandrika J, AU - Macaluso,Maurizio, AU - Chambers,Michelle M, AU - Badiga,Suguna, AU - Siddiqui,Nuzhat R, AU - Bell,Walter C, AU - Edberg,Jeffrey C, AU - Partridge,Edward E, AU - Alvarez,Ronald D, AU - Johanning,Gary L, Y1 - 2014/08/21/ PY - 2014/8/23/entrez PY - 2014/8/26/pubmed PY - 2015/7/24/medline SP - 1128 EP - 37 JF - Cancer prevention research (Philadelphia, Pa.) JO - Cancer Prev Res (Phila) VL - 7 IS - 11 N2 - We previously reported that a higher degree of methylation of CpG sites in the promoter (positions 31, 37, 43, 52, and 58) and enhancer site 7862 of human papillomavirus (HPV) 16 was associated with a lower likelihood of being diagnosed with HPV 16-associated CIN 2+. The purpose of this study was to replicate our previous findings and, in addition, to evaluate the influence of plasma concentrations of folate and vitamin B12 on the degree of HPV 16 methylation (HPV 16m). The study included 315 HPV 16-positive women diagnosed with either CIN 2+ or ≤CIN 1. Pyrosequencing technology was used to quantify the degree of HPV 16m. We reproduced the previously reported inverse association between HPV 16m and risk of being diagnosed with CIN 2+. In addition, we observed that women with higher plasma folate and HPV 16m or those with higher plasma vitamin B12 and HPV 16m were 75% (P < 0.01) and 60% (P = 0.02) less likely to be diagnosed with CIN 2+, respectively. With a tertile increase in the plasma folate or vitamin B12, there was a 50% (P = 0.03) and 40% (P = 0.07) increase in the odds of having a higher degree of HPV 16m, respectively. This study provides initial evidence that methyl donor micronutrients, folate and vitamin B12, may play an important role in maintaining a desirably high degree of methylation at specific CpG sites in the HPV E6 promoter and enhancer that are associated with the likelihood of being diagnosed with CIN 2+. SN - 1940-6215 UR - https://www.unboundmedicine.com/medline/citation/25145486/full_citation L2 - http://cancerpreventionresearch.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=25145486 DB - PRIME DP - Unbound Medicine ER -