The Basal Study Of Protein Expression Of XRCC1 And MGMT In Sporadic Colorectal Carcinoma

Background & Objective: Colorectal cancer is among the most common malignant tumor in the world, with morbidity rising in China gradually.More than 90% of the colorectal carcinoma generates sporadically, as the outcome of interactions between the environmental and genetic factor, involving the change of multiple genes. The colorectal carcinogenesis mainly occurs in 3 categories cellular genes, i.e. cancer suppressor gene,oncogene, DNA repair gene.Food contacts immediately with the colorectum and affects it strongest as one of the environmental agents. Among those food, nitrosamines com- pounds are common alimentary tract carcinogen,forming bulky adducts with DNA. The repair of DNA adducts chiefly depend on the base excision repair and direct restoration repair.Human X-ray repair cross-complementing gene 1 (XRCC1) participates in base excision repair and repair of single-strand breaks caused by ionizing radiation or reactive oxygen agent. Abnormal ex- pression of XRCC1 is related to multiple carcinogenesis. Domestic current research mainly focused on the distribution of its different genotype in tumor and normal tissue in order to analyze the individual tumor susceptibi- lity,while the protein expression of XRCC1 was described little. O6-methyl- guanine-DNA-methyltransferase (MGMT) protects cells from various mutagen and carcinogen attacks by transferring the alkyl groups from the O6 position of guanine to a cysteine in its active site without base excision. Meanwhile the enzyme loses its activity. Now DNA repair- deficiency is considered to contribute to tumorigenesis in the initial stage.Our trial has assessed the protein expression of XRCC1 and MGMT, analyzed the relationship among them and clinical parameters. We alsodiscussed the feasibility whether the cause for colorectal carcinogenesis and its malignant biological behavior can be presumed through immunohisto- chemistry technique.Methods: The paraffin specimen from 95 colorectal cancer patients and 49 normal control patients was made into tissue assay. SP method of immuno- histochemistry was utilized to detect the protein expression of XRCC1 and MGMT. Statistic software SPSS13.0 was used to analyze the relationship between their expressions and clinical feature.Results:1. XRCC1 protein mainly expressed in cellular nuclei. The expres- sion in colorectal cancer group and control group was 85.3% (81/95) and 44.9% (22/49) respectively. There was significant difference between the carcinoma group and the control group (P=0.000).In high-moderate grade and low-grade differentiation, the expression percent was 83.1% (59/71) and 90.0% (18/20) respectively. No statistic significance existed (P=0.686). The expression percent was 80.7% (46/57) and 92.1% (35/38) respectively in T1+T2 group and T3+T4 group, P=0.125, with no statistic significance. The positive ratio was 82.9%(29/35)and 86.7%(52/60) respectively in group with and without lymph node metastasis, with no statistic difference(P= 0.613). 100.0% (14/14) in group with distant metastasis and 85.0% (69/81) in that without distant metastasis, P=0.269. There was no relationship between them. XRCC1 expression had no relationship with the age and gender.2.MGMT expressed mainly in the cytoplasm. The expression in colorectal can- cer group and control group was 43.2% (41/95) and 12.2% (6/49) respectively. There was significant difference between the carcinoma group and control group (P=0.000). In high-moderate grade and low-grade differentiation, the expression percent was 46.5% (33/71) and 30.0% (6/20) respectively. No statistic significance existed (P=0.188).The expression percent was 38.6% (22/57) and 50.0% (19/38) respectively in T1+T2 group and T3+T4 group, P=0.272,with no statistic significance. The positive ratio was 42.9% (15/35) and 43.3% (26/60) respectively in group with and without lymph node metastasis.50.0% (7/14) in group with distant metasta- sis and 42.0% (34/81) in that without distant metastasis. There was no rela-tionship between them. MGMT expression had no relationship with the age and gender.3. The correlation coefficient of XRCC1 and MGMT equaled to 0.242, P=0.018. There was positive correlation between them.Conclusions:1. The expression level of XRCC1 might represent the DNA injury degree in the colorectal carcinoma tissue and become one of the indexes predicting the malignant behavior of colorectal carcinoma.2. Inhibition of XRCC1 expression in the colorectal cancer tissue might enhance its susceptibility to radiotherapy or chemotherapy.3.The expression level of MGMT might represent the DNA injury degree in the colorectal carcinoma tissue and become one of the indexes predicting the malignant behavior of colorectal carcinoma.4. The elevated expression of XRCC1 and MGMT in malignant colorectal behavior might relate to the growing AP sites.