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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2010;3(1):xxx-xxx.
Original Article
Amino acid substitution polymorphisms of O6-Methylguanine DNA
Methyltransferase and susceptibility to sporadic colorectal cancer
Fatemeh Khatami, Seyed Reza Fatemi, Somayeh Ghiasi, Sepideh Shivarani, Mohammad Reza Zali
Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of medical Science, Tehran, Iran
Received November 7, 2009; accepted December, 2009; available online January 1, 2010
Abstract: Sporadic colorectal cancer is the fourth most common cancer in Iran. The DNA repair protein O6-methylguanine-DNA
methyltransferase (MGMT) is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may
impair the protein’s ability to remove alkyl groups from the O6-position of guanine, thereby raising the mutation rate and increasing the
risk of sporadic colorectal cancer. We hypothesized that amino acid substitution polymorphisms in the MGMT gene may be associated
with the genetic susceptibility to sporadic colorectal cancer. We assessed five non-synomymous polymorphisms (Pro58Ser,
Leu84Phe, Arg128Gln, Ile143Val, Gly160Arg) in the MGMT gene by PCR/Pyrosequencing. The population studied consisted of 200
sporadic colorectal cancer patients and 200 healthy individuals (blood donors),both of Iranian origin. Allele frequencies and genotypes
were compared between the cases and controls. Odds ratios were calculated and the interaction between the polymorphisms, age
and sex were examined. There was a significant association between two amino acid substitution polymorphisms (Arg128Gln and
Gly160Arg) of MGMT gene and sporadic colorectal cancer. We could show significant association between two polymorphisms and
colorectal cancer. Larger sets of sample sizes are required support our finding possibility of association between these two
polymorphisms and colorectal cancer. (IJCEM911003).
Key words: O6-methylguanine-DNA methyltransferase (MGMT) , amino acid substitution polymorphisms , Pyrosequencing
Full Text PDF
Address all correspondence to:
Fatemeh Khatami, MD
Research Center for Gastroenterology and Liver Disease
Shahid Beheshti University of medical Science
Tehran, Iran
Tel: +982122418872, 22402639
Fax: +98212402639
Email : Khatam81@yahoo.com
Original Article
Amino acid substitution polymorphisms of O6-Methylguanine DNA
Methyltransferase and susceptibility to sporadic colorectal cancer
Fatemeh Khatami, Seyed Reza Fatemi, Somayeh Ghiasi, Sepideh Shivarani, Mohammad Reza Zali
Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of medical Science, Tehran, Iran
Received November 7, 2009; accepted December, 2009; available online January 1, 2010
Abstract: Sporadic colorectal cancer is the fourth most common cancer in Iran. The DNA repair protein O6-methylguanine-DNA
methyltransferase (MGMT) is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may
impair the protein’s ability to remove alkyl groups from the O6-position of guanine, thereby raising the mutation rate and increasing the
risk of sporadic colorectal cancer. We hypothesized that amino acid substitution polymorphisms in the MGMT gene may be associated
with the genetic susceptibility to sporadic colorectal cancer. We assessed five non-synomymous polymorphisms (Pro58Ser,
Leu84Phe, Arg128Gln, Ile143Val, Gly160Arg) in the MGMT gene by PCR/Pyrosequencing. The population studied consisted of 200
sporadic colorectal cancer patients and 200 healthy individuals (blood donors),both of Iranian origin. Allele frequencies and genotypes
were compared between the cases and controls. Odds ratios were calculated and the interaction between the polymorphisms, age
and sex were examined. There was a significant association between two amino acid substitution polymorphisms (Arg128Gln and
Gly160Arg) of MGMT gene and sporadic colorectal cancer. We could show significant association between two polymorphisms and
colorectal cancer. Larger sets of sample sizes are required support our finding possibility of association between these two
polymorphisms and colorectal cancer. (IJCEM911003).
Key words: O6-methylguanine-DNA methyltransferase (MGMT) , amino acid substitution polymorphisms , Pyrosequencing
Full Text PDF
Address all correspondence to:
Fatemeh Khatami, MD
Research Center for Gastroenterology and Liver Disease
Shahid Beheshti University of medical Science
Tehran, Iran
Tel: +982122418872, 22402639
Fax: +98212402639
Email : Khatam81@yahoo.com
