Linked Life Data

15583437

Source:http://linkedlifedata.com/resource/pubmed/id/15583437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-12-7
pubmed:abstractText
Progress in the elucidation of molecular genetic changes that lead to the development of tumors should soon bring novel diagnostic and therapeutic procedures into clinical practice. In this respect, methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism that affects DNA methylation and synthesis. DNA methylation is an epigenetic feature that influences cellular development and function. Germ line mutation C>T at nucleotide 677 of the MTHFR gene, which results in increased thermolability and diminished enzyme activity, is oncogenic, i.e. should be a contributor to molecular changes leading to cancerous phenotypes (it has also been shown independently to be implicated in cardiovascular disease phenotypes). Interestingly, it has been shown that MTHFR T677 allele homozygosity confers a sixfold increased risk for esophageal squamous cell carcinoma in Northern China. The purpose of this study was twofold: (1) to evaluate the putative association of MTHFR C677T and epithelial squamous cell carcinoma (ESCC) in Pakistan, and (2) to investigate whether de novo MTHFR C677T mutations are involved in the determination of ESCC phenotypes. We recruited 50 ESCC patients referred to the Otolaryngology Clinic of the Aga Khan University Hospital, and 54 age- and gender-matched control (disease-free) subjects. Our results show that T allele frequencies were 0.18 +/- 0.05 in cases vs. 0.24 +/- 0.05 in controls (as compared with 0.63 vs. 0.41 in the report from China). Although the association is not statistically significant, T alleles are actually more common amongst controls in the Pakistani population, which is the opposite of what would be expected and what has been reported amongst Chinese. Yet the frequency of deleterious T alleles is lower in Pakistan (range 0.18-0.24) than in other parts of the world. Our results indicate that MTHFR C677T cannot form the basis for a genetic test aimed at evaluating an individual's genetic susceptibility to ESCC in Pakistan. As the conversion of precancerous submucous fibrosis into overt cancer is a frequent occurrence in Pakistan, we proceeded to extract DNA samples in all ESCC patients, from whole blood, cancerous tissues and neighboring normal tissues. We sought to determine whether C677T genotypes were different in the three tissue samples from each ESCC patient. In all patients, identical genotypes (and therefore allele frequencies) were systematically observed in all three samples. This indicates that de novo MTHFR 677TC>T mutations are not part of the molecular etiology of ESCC. In conclusion, we can rule out a major involvement of the MTHFR gene in the determination of ESCC in Pakistan.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0301-1569
pubmed:author
pubmed:copyrightInfo
Copyright 2004 S. Karger AG, Basel.
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
241-5
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Head and neck cancer susceptibility: a genetic marker in the methylenetetrahydrofolate reductase gene.
pubmed:affiliation
Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.
pubmed:publicationType
Journal Article