Study On The Single Nucleotide Polymorphisms Within Tumor Suppressor Genes Of Colorectal Carcinoma

Chapter One The association between the XRCC1 Arg399Gln polymorphism and susceptibility to sporadic colorectal carcinomaObjective A case-control study was conducted pertaining a single nucleotide polymorphism of XRCC1 gene from candidate region of 19q13.2 to assess its allele distribution and its association with both sporadic colorectal carcinoma and its pathological characters.Methods DNA was extracted from both cancerous tissue of 178 incident cases and blood samples of 180 non-carcinoma controls, then real-time Taqman analyses were conducted to genotype each subject. The statistical analysis software SHESIS and SAS were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI).Results There were significant discrepancies in the distribution of genotype frequencies both between cases and controls (P<0.05)and between the cases who were under 60 years of age and the cases who were above (P<0.05). Moreover, the inheritance of 399 Gln allele (combined Arg/Gln and Gln/Gln genotype) was associated with reduced risk of colorectal carcinoma in both of those who were above the age of 50 (OR=0.64, 95% CI 0.50-0.83, P<0.05) and the male subjects (OR=0.64, 95% CI 0.51-0.79, P< 0.05). However, no significant association of XRCC1 Arg399Gln polymorphism was observed with either clinical or pathological characters concerning sex, tumor location, Dukes stages, depth of penetration, lymph node metastasis and pathological subtypes (P>0.05).Conclusion XRCC1 Arg399Gln polymorphism can be a risk factor for sporadic colorectal carcinoma and may be associated with an altered DNA repair proficiency, which leads to an increase of susceptibility.Chapter two The impact of MCC gene 511 polymorphism on the lymph node metastasis of sporadic colorectal carcinomaObjective A case-control study was conducted pertaining a single nucleotide polymorphism of MCC gene from candidate region of 5q21 to assess its allele distribution and its association with both sporadic colorectal carcinoma and pathological characters.Methods DNA was extracted from both cancerous tissue of 172 incident cases and blood samples of 180 non-carcinoma controls, then real-time Taqman analyses were conducted to genotype each subject. The statistical analysis software SHESIS and SAS were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI).Results The genotype(T/T, T/C, C/C) distribution of the MCC gene 511 SNP in the patients with colorectal carcinoma(CRC) was not significantly different compared with that in non–carcinoma controls(P>0.05). When stratified for age and sex respectively, compared with T/T genotype, combination of T/C and C/C genotypes of MCC gene 511 SNP had no significant influence on the risk of developing CRC. A significant association has been found between the MCC gene 511 polymorphism and the lymph node metastasis (P<0.05). However, there was no significant association of MCC gene 511 polymorphism observed with either clinical or pathological characters concerning sex, age, Dukes stages, depth of penetration, and pathological subtypes (P>0.05).Conclusion MCC gene 511 SNP may play a role in the lymph node metastasis and promote the progression of CRC by causing the deletion of this gene of interest and its adjacent region on the chromosome 5.Chapter Three The link between DCC gene 201 polymorphism and the penetration of sporadic colorectal carcinomaObjective A case-control study was conducted pertaining a single nucleotide polymorphism of MCC gene from candidate region of 18q21 to assess its allele distribution and its association with both sporadic colorectal carcinoma and pathological characters.Methods DNA was extracted from both cancerous tissue of 174 incident cases and blood samples of 179 non-carcinoma controls, then real-time Taqman analyses were conducted to genotype each subject. The statistical analysis software SHESIS and SAS were applied to process all statistical data.Results The genotype(Arg/Arg, Arg/Gly, Gly/Gly) distribution of the DCC gene 201 SNP in the patients with colorectal carcinoma(CRC) was not significantly different compared with that in non–carcinoma controls(P>0.05). A significant association has been found between the DCC gene 201 polymorphism and the depth of penetration(P<0.05). However, there was no significant association of DCC gene 201 polymorphism observed with either clinical or pathological characters concerning sex, age, Dukes stages, lymph node metastasis, and pathological subtypes (P>0.05).Conclusion The amino substitution caused by the DCC gene 201 polymorphism may affect the its capacity to induce programmed cell death through cell signal transduction pathways, thus the invasiveness of the malignant cell may increase and the penetration of carcinoma may be deepened.