A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis

Gautam G. Rao, Aleena Kurien, Diana Gossett, William F. Griffith, Robert L. Coleman, Carolyn Y. Muller

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objectives.: Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are thought to be associated with a varying risk of cervical dysplasia. The purpose of this trial was to study the role of the two common functional MHTFR polymorphisms in a large multiracial population at risk for cervical dysplasia and cancer. Methods.: This is a nested case-control study of 376 subjects obtained from cohorts enrolled in an ongoing prospective cervical carcinogenesis protocol. Cases included invasive cancers (n = 51), and high (n = 50) and low (n = 50) grade dysplasia. There were 225 normal controls. Functional MTHFR 677C→T and 1298A→C genotypes were identified. Follow-up cytology data were reviewed for the control subjects from the time of study entry until August 2004. Results.: There is a significant racial difference in allele frequency of the 677C→T polymorphism (P < 0.005). African-American women had an extremely low prevalence of the 677T allele (8%). There was no significant difference in the frequency of the 677T allele between cases and controls. There is no racial difference in allele frequency of the 1298A→C polymorphism. Also, no significant difference was found between cases and controls. Of the 51 cancers, no case was homozygous for both aberrant polymorphisms (677T, 1298C), and only 3 cases were heterozygous for both. Follow-up data were available for 129 of 225 control subjects (57%). Only 15 (12%) have had a subsequent abnormal pap, and there was no association with the 677C→T polymorphism. Conclusions.: We confirm a significant difference in the 677T allele frequencies among racial groups. However, there is no association of either the 677C→T or 1298A→C polymorphisms in cervical carcinogenesis. There is no role of the combined polymorphism effect in cervical cancer or evidence of prediction for future Pap abnormalities.

Original languageEnglish (US)
Pages (from-to)250-254
Number of pages5
JournalGynecologic oncology
Volume101
Issue number2
DOIs
StatePublished - May 1 2006

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Keywords

  • Cervical cancer
  • Folic acid
  • Methylenetetrahydrofolate reductase

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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