title: Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt.
abstract: An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Soliman
authors.forename: M L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.forename: S
authors.initials: S
authors.lastname: El-Badawi
authors.forename: N
authors.initials: N
authors.lastname: Mokhtar
authors.forename: S
authors.initials: S
authors.lastname: Bayomi
authors.forename: A A
authors.initials: AA
authors.lastname: Raouf
authors.forename: S
authors.initials: S
authors.lastname: Ismail
authors.forename: R S
authors.initials: RS
authors.lastname: McPherson
authors.forename: T F
authors.initials: TF
authors.lastname: Abdel-Hakim
authors.forename: R P
authors.initials: RP
authors.lastname: Beasley
authors.forename: B
authors.initials: B
authors.lastname: Levin
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000328:Adult; D000367:Age Factors; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics; D004534:Egypt / Q000453:epidemiology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes