Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-12-25
pubmed:abstractText
Epidemiological studies have been inconsistent regarding a role for folate in the etiology of cervical dysplasia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, which is involved in the methylation of homocysteine to methionine. A common variant of this enzyme, resulting from a 677C-->T (Ala-->Val) substitution in the gene, has been shown to have reduced activity and is associated with mild hyperhomocysteinemia. A multiethnic case-control study was used to examine the association of dietary folate and MTHFR genotype with the odds ratios (ORs) for cervical dysplasia among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. We collected blood samples for DNA extraction, cervical smears for cytological diagnosis, exfoliated cervical cells for human papillomavirus (HPV) DNA testing, and personal interviews from 150 women with squamous intraepithelial lesions (SILs) and from 179 women with cytologically normal (Pap) smears. We found a positive, monotonic trend (P = 0.02) in the ORs for cervical SILs associated with the number of variant MTHFR T alleles, after multivariate adjustment. Women with the heterozygous CT genotype had twice the risk of cervical SILs [OR, 2.0; 95% confidence interval (CI), 1.1-3.7], and women with the homozygous TT genotype had almost three times the risk of SILs (OR, 2.9; 95% CI, 1.0-8.8) compared to women with the homozygous MTHFR CC genotype. The dietary intakes of folate, vitamin B(6), and vitamin B(12) were inversely related to the ORs for cervical SILs, after adjustment for HPV DNA and other confounders. The OR among women in the highest quartile compared with women in the lowest quartile of folate intake was 0.3 (95% CI, 0.1-0.7; P for trend = 0.002). Women with the variant T allele and folate intakes below the median were at significantly elevated risk of cervical SILs (OR, 5.0; 95% CI, 2.0-12.2) compared to women with CC alleles and folate intakes above the median. HPV infection was a strong risk factor for cervical dysplasia, particularly among women with the variant T allele (OR, 46.6; 95% CI, 15.9-136.2). All associations of MTHFR genotype with the ORs for cervical SILs were independent of other risk factors under study. These findings suggest that the MTHFR T allele and reduced dietary folate may increase the risk for cervical SILs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1275-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11751445-Adult, pubmed-meshheading:11751445-Case-Control Studies, pubmed-meshheading:11751445-DNA, Viral, pubmed-meshheading:11751445-Diet, pubmed-meshheading:11751445-Epidemiologic Studies, pubmed-meshheading:11751445-Ethnic Groups, pubmed-meshheading:11751445-Female, pubmed-meshheading:11751445-Folic Acid Deficiency, pubmed-meshheading:11751445-Genotype, pubmed-meshheading:11751445-Humans, pubmed-meshheading:11751445-Methylenetetrahydrofolate Reductase (NADPH2), pubmed-meshheading:11751445-Odds Ratio, pubmed-meshheading:11751445-Oxidoreductases Acting on CH-NH Group Donors, pubmed-meshheading:11751445-Papillomaviridae, pubmed-meshheading:11751445-Papillomavirus Infections, pubmed-meshheading:11751445-Polymorphism, Genetic, pubmed-meshheading:11751445-Precancerous Conditions, pubmed-meshheading:11751445-Risk Factors, pubmed-meshheading:11751445-Tumor Virus Infections, pubmed-meshheading:11751445-Uterine Cervical Neoplasms, pubmed-meshheading:11751445-Vaginal Smears
pubmed:year
2001
pubmed:articleTitle
Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia.
pubmed:affiliation
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA. marc@crch.hawaii.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.