A relationship between methylenetetrahydrofolate reductase variants and the development of invasive cervical cancer. Gynecol Oncol 2003 Sep;90(3):560-5
Date
09/19/2003Pubmed ID
13678724DOI
10.1016/s0090-8258(03)00368-8Scopus ID
2-s2.0-0141974970 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
OBJECTIVE: Low red blood cell folate levels have been associated with hypomethylation of DNA in dysplastic tissue and an increased risk for cervical intraepithelial neoplasia in human papillomavirus (HPV)-infected women. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating the metabolism of folate and methionine, the important components of DNA synthesis and methylation. Two common genetic polymorphisms, causing reduced MTHFR activity, have been identified. Therefore, the goal of this study was to evaluate these MTHFR variations as risk factors for invasive cervical cancer.
METHODS: To overcome the failure to properly match cases and controls that can cause false-positive inferences due to population stratification and unrecognized variables in a traditional case-control study, a family-based transmission/disequilibrium test (TDT) was used. We obtained samples from nuclear families of 102 women with invasive cervical cancer (ICC). One polymorphism was typed by a PCR-RFLP method, while a template-directed dye-terminator assay was developed for the other.
RESULTS AND CONCLUSIONS: We were unable to confirm a strong association of MTHFR polymorphisms and ICC using family-based controls and a transmission/disequilibrium test. The overall results of the TDT showed chi(2) (1 df) of 0.28 (P = 0.60) for exon 4, chi(2) (1 df) of 0.81(P = 0.37) for exon 7, and chi(2) (3 df) of 2.56 (P = 0.46) for the haplotype, meaning that there was no transmission of those alleles significantly in excess of Mendelian expectations to affected women. In addition, there was no effect of these variants with increased parity or infection with high-risk-type human papillomavirus.
Author List
Gerhard DS, Nguyen LT, Zhang ZY, Borecki IB, Coleman BI, Rader JSAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAlleles
Female
Humans
Linkage Disequilibrium
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Oxidoreductases Acting on CH-NH Group Donors
Polymorphism, Genetic
Uterine Cervical Neoplasms