REDUCED EXPRESSION OF MISMATCH REPAIR GENES IN COLORECTAL-CANCER PATIENTS IN EGYPT

An Egyptian hospital-based pilot case-control study was conducted to i nvestigate the relationship between the expression level of mismatch r epair (MMR) genes and the risk of colorectal cancer. The relative expr ession of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-pol ymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 c olorectal cancer patients and 47 age-and-sex matched controls. The exp ression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in pa tients than controls, but only the difference in hPMS2 expression was statistically significant (p<0.01). Although 50% of the cases had chem otherapy or radiotherapy within the last six months before the blood w as drawn, their gene expression was not statistically different from t hose who had not undergone such therapies. After adjustment for age an d sex, the odds ratios (OR) calculated from a logistical regression mo del, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced exp ressions 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 r esults of this study were inconclusive because of the small sample siz e and use of prevalent cases, it is biologically plausible that patien ts with colorectal cancers may have a lower expression of MMR genes th an 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 pop ulation. Further studies with newly diagnosed patients before they beg in therapy will provide more convincing data about the role of MMR gen e expression in the etiology of colorectal cancers in Egypt.