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Title: Polymorphisms of Folate Metabolizing Genes in Colorectal Cancer in Kashmiri population
Researcher: Qazi, Falak
Guide(s): Ganai, Bashir Ahmad and Chowdri, Nisar Ahmad
University: University of Kashmir
Completed Date: 2014
Abstract: Folate s important biological function is to provide single carbon units (methyl newlinegroups) required for intracellular methylation reactions and de novo DNA and newlineamino acid metabolism (biosynthesis of methionine, thymidylate, purines, and newlineglycine, and in the metabolism of serine, formate, and histidine) which proceeds newlinethrough folate /one carbon metabolism pathway (FOCM). Polymorphic variants in newlineone-carbon metabolism genes may modulate risk of colorectal cancer through newlineaberrant DNA methylation and altered nucleotide synthesis and repair. Thymidylate newlineSynthase catalyzes an important reaction for cell proliferation (reductive newlinemethylation of dUMP by 5, 10-methylene tetrahydrofolate to form dTMP; which is newlinethe sole de novo source of thymidine and the rate limiting step in DNA synthesis in newlinemammalian cells. Thus is a crucial substrate in folate metabolism with connections to three biosynthetic pathways: thymidine synthesis, purine synthesis, or methionine synthesis. The reduced folate carrier (RFC) actively transports folate compounds into cells from the plasma and plays a role in maintaining intracellular newlineconcentrations of folate. TS is also an important drug target for chemotherapeutic newlineagents while as these agents are preferably transported by RFC. newlineOur study was to investigate prospectively the association of the TS and RFC gene newlinepolymorphisms with colorectal cancer in Kashmiri population. The study was newlineperformed on a total of 421 subjects that comprised of 200 colorectal cancer patients newlineand 221 normal subjects. The TS gene was assessed for the variation in a 28 bp newlinetandem repeat sequence present in the 5 UTR region and RFC gene for (an newlinearginine- histidine substitution) polymorphism in exon 2 at position 80. For TS gene newlinewe observed that 3R allele was most commonly present in cases with a frequency of newline54.25 % and 52.04% in controls while as 2R allele was more common in controls newlinewith a frequency of 47.96% and 45.75% in cases. Still none of the two alleles either newline3R or 2R were found to be significantly associated with CRC.....
Appears in Departments:Department of Biochemistry

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01_ title.pdfAttached File173.25 kBAdobe PDFView/Open
02_certificates.pdf259.14 kBAdobe PDFView/Open
03 _acknowledgements.pdf54.46 kBAdobe PDFView/Open
04_dedication.pdf88.1 kBAdobe PDFView/Open
05_contents.pdf30.26 kBAdobe PDFView/Open
06_abbrevations.pdf44.14 kBAdobe PDFView/Open
07_ list _of_tables.pdf44.51 kBAdobe PDFView/Open
08_list_of_ figures.pdf46.96 kBAdobe PDFView/Open
09_abstract.pdf78.12 kBAdobe PDFView/Open
10_chapter1.pdf116.55 kBAdobe PDFView/Open
11_chapter2.pdf550.89 kBAdobe PDFView/Open
12_chapter3.pdf147.11 kBAdobe PDFView/Open
13_chapter4.pdf344.5 kBAdobe PDFView/Open
14_chapter5.pdf120.14 kBAdobe PDFView/Open
15_conclusion.pdf84.2 kBAdobe PDFView/Open
16_bibliography.pdf235.34 kBAdobe PDFView/Open

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