Mutational analysis of the MTHFR gene in breast cancer patients of Pakistani population.
OBJECTIVE
Since methylenetetrahydrofolate reductase (MTHFR) maintains the balance of circulating folate and methionine and blocks the formation of homocysteine, its regulation in relation to different cancers has extensively been studied in different populations. However, information on Pakistani breast cancer patients is lacking. The MTHFR gene has two most common mutations that are single nucleotide additions which result in change of amino acids C677T to Ala222val and A1298C to Glu429Ala.


METHODS
110 sporadic breast patients with no prior family history of cancer or any other type of genetic disorders along with 110 normal individuals were screened for mutations in exons 1 to exon 9 using single strand conformational polymorphism, RFLP and sequencing analyzer.


RESULTS
The p values for the 677CC, 677CT, and 677TT genotypes were 0.223, 0.006, and 0.077, respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 0.555, 0.009, and 0.003, respectively.


CONCLUSIONS
We found an overall a significant, weak inverse association between breast cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR polymorphism might be population specific in sporadic breast cancer affected patients but many other factors need to be excluded before making final conclusions including folate intake, population and disease heterogeneity.
Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
Muhammad
M
Akram
F A
FA
Malik
Mahmood Akhtar
MA
Kayani
D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010154:Pakistan; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational
C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)