Polymorphisms Of GSTM1,GSTT1 And GSTP1 And Susceptibility Of Colorectal Cancer

【Background】Colorectal cancer(CRC)is one kind of the most common malignant digestive tract cancers in the world. It has been estimated that there are more thanS00, 000 new cases each year, and that the CRC is the third most common cancer(after lung and stomach) worldwide and the second One in developed countries(after lung). China is a nation with a relatively low incidence of CRC, which is the fifth or sixth most common cause of cancer death. But recently the incidence rate of CRC has increased especially in the developing world with the change to western dietary. According to data from the investigate of malignant tumors, in 1994, the mortality of CRC was 8.96 per 100, 000 in big city, and in rural it was5.47 per 100, 000. Compared with that in 1988 CRC moryality was increased by 3ï¼…in rural area, but 15ï¼…in big city.The incidence of CRC is a scribed to multiple factors and stages. Worldwide, the incidence rates vary approximately 80-fold between American(the highest) and India(the lowest), which could be explained by the environmental factors especially diet factors and the genetic susceptibility. Glutathione S-transferases(GST) are the important of the second stage enzymes in human body, they are responsible for the efficient modification of harmful molecules, making them less biologically active and facilitating their excretion. Therefore, polymorphisms in the detoxification enzymes may be contribute to individual susceptibility to CRC.Recently, many studies have focused on the relationship between the genetic polymorphisms and risks of CRC. However, the overall results of such studies are inconsistent.【Objective】We conducted apopulation-based case-control study in Jiangsu province to explored the distribution of genetic polymorphisms of GSTM1,GSTT1 and GSTP1 in normal population. Furthermore, to study the relationship between genetic polymorphisms of GSTM1,GSTT1 and GSTP1 and the susceptibility of CRC.【Methods】We analyzed data from the case-control studies conducted in jiangsu: a population-based study of 315 case patients with colorectal cancer and 439 control subjects during August 2000 to September 2002. All subjects were interviewed face-to-face by trained interviewers. For each smoking and alcohol drinking, amounts consumed were estimated according to models of the more frequently consumed smoking and alcohol drinking for the accuracy of survey. Blood samples were taken at the time of interview or shortly after and stored at-30 Centigrade degrees(C) refrigerator. Genomic DNA was extracted from whole frozen blood samples using improved salting out procedure. The laboratory assays was organized two parts. Part One: Genotypes of the GSTM1 and GSTT1 were detected by multiplex PCR, to reveal the relationship between the genetic polymorphism of GSTM1,GSTT1 and the susceptibility of CRC. Part Two: Polymorphism of the GSTP1 A→G was detected using PCR-based restriction fragment length polymorphisms(PCR-RFLP) with Alw26I, to explore the relationship between the genetic polymorphism of GSTP1 and the susceptibility of CRC. The statistical analysis used unconditional logistic regression to adjust odds ratios(OR) for the matching variables(age, sex), as well as for the variables found to be associated with risk. Theχ² test was used to compare the observed genotype distributions with those expected by the Hardy-Weinberg equilibrium. All analyses were performed with SAS and Excel 2000. All statistical tests are two-sided.【Results】1) No significant difference was found in prevalence of GSTM1 genotypes deletion among the patients and controls(72.70ï¼…,73.29ï¼…respectively)(χ²_MH=0.032, P=0.857). Individuals who had GSTM1 genotypes deletion were at no increased risk of CRC(adjusted for age, sex and status of the smoking and alcohol drinking(OR=1.03, 95ï¼…CI: 0.74-1.43). 2) No significant difference was found in prevalence of GSTT1 genotypes deletion among the patients and controls(55.24ï¼…,57.31ï¼…respectively) (χ²_MH=0.318, P=0.573). Individuals who had GSTT1 genotypes deletion were at no increased risk of CRC (adjusted for age, sex and status of the smoking and alcohol drinking (OR=1.08, 95%CI: 0.80～1.45). 3) the frequencies of the GSTP1 A/A, A/G and G/G genotypes distribution were 57.51%,36.74% and 5.75% in patients, and 63.70%,31.05% and 5.25% in controls respectively, with no significantly different (X²_MH=2.993, P=0.224). Individuals who had GSTP1 G/G genotypes were at no increased risk of CRC (adjusted for age, sex and status of the smoking and alcohol drinking (OR=1.09, 95%CI: 0.79～1.51) compared with those with GSTP1 A/A genotypes. The distributions of the genotypes was consistent with the Hardy-Weinberg equilibrium.【Conclusions】The polymorphisms of GSTM1,GSTT1 and GSTP1 has no relationship with the susceptibility of CRC in Jiangsu Province.