[ effect of o6-methyl guanine methyl teranferase in colorectal cancer]

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], all of Iranian origin. Allele frequencies and genotypes were compared between the two groups. Odds ratios were calculated and the interactions among 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 a significant association between the two polymorphisms and colorectal cancer. This might be a superior marker for colon cancer screening in the future