The Association Of ST13 Polymorphism With The Risk Of Colorectal Cancer

Objective: ST13 gene (Suppression of Tumorgenecity13 Gene) is a negatively related gene of Colorectal Cancer(CRC) discovered by subtractive hybridization. The pritein encoded by the ST13 gene was considered as an Hsp70-specific positive co-chaperone to play an important role in protein folding and in controlling the activity of regulatory proteins and might correlate with the occurrence and development of cancer.The genetic polymorphisms of ST13 gene might be able to influence the gene transcription and expression at the protein level, which might affect the individual tumor susceptivity further.T he study was designed to investigate the correlation of ST13 rs5758098A/G,rs138335 G/C,rs138344C/G SNPs with the risk of CRC. By this way, we hope to offer some evidences for the prevention and therapy of CRC at melocularbiological level.Methods: This population-based case-control study included 200 CRC patients and 200 heaalthy controls. The genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Genotypes of the ST13 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Statistical analysis was performed using SPSS11.5 software package. A probability level of 5% was considered significant for all statistical analyses. The age difference of cases and frequency-matched controls was analyzed by the t-test,while the analysis of the gender difference between cases and controls used Chi-square test. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the ST13 genotype and allelotype distribution in patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression model.Results:1 The genotype frequencies of ST13 rs5758098A/G, rs138335G/C and rs138344C/G in healthy controls did not significantly deviate from that expected for a Hardy-Weinberg equilibrium (P>0.05).2 The frequencies of the ST13 rs5758098A/G A and G allele among CRC pa- tients and healthy controls were 84.3%,15.7% and 83.0%,17.0% respectiv- ely; No significant difference in the ST13 rs5758098A/G allele distributio- n was shown between CRC patients and controls (P>0.05); The distribut- ion of the A/A, A/G and G/G genotypes between CRC patients (69.0%, 30.5% and 0.5%, respectively) and controls (70.5%, 25.0% and 4.5%,resp ectively) had significant difference (P<0.05). Compared with the A/A gen otype, the A/G and G/G genotypes could significantly increase the risk of CRC, the odds ratio were 8.600 (95%CI=1.070~69.089) and 10.671 ( 9 5%CI=1.299~87.647). When stratified for smoking status, the A/G and G/G genotypes significantly increase the risk of developing CRC among non-s- moking patients compared with the A/A genotype with the OR of 8.175(95%CI=1.015~65.871) and 10.939(95%CI=1.318~90.802) respectively. When stratified for drinking status, the A/G and G/G genotypes also significantly increase the risk of developing CRC among non-drinking pa- tients compared with the A/A genotype with the OR of 8.427( 9 5%CI=1.046~67.880) and 11.554(95%CI=1.396~95.645) respectively.3 The frequencies of the ST13 rs138335G/C G and C allele among CRC pat- ients and healthy controls were 51.2%, 48.8% and 47.0%, 53.0% respecti- vely; No significant difference in the ST13 rs138335G/C allele distribution was shown between CRC patients and controls (P>0.05). The distribution of the G/G, G/C and C/C genotypes between CRC patients (27.5%, 47.5% and 25.0%, respectively) and controls (25.5%, 43.0% and 31.5%,respectiv- ely) also had no significant differrence (P>0.05). Compared with the G/G genotype, the G/C and C/C genotypes could not increase the risk of devel- oping CRC, the odds ratio were 1.360 (95%CI=0.798~2.315) and 1.389( 95%CI=0.866~2.228).When stratified for smoking and drinking status, no significant difference in genotype and allele distributions was found betw- een patients and control groups in ST13 rs138335G/C (P>0.05).4 The frequencies of the ST13 rs138344C/G C and G allele among CRC pat- ients and healthy controls were 91.8%, 8.2% and 94.0%, 6.0% respectively; No significant difference in the ST13 rs138344C/G allele distribution was shown between CRC patients and controls (P>0.05). The distribution of the C/C, C/G and G/G genotypes between CRC patients (85.5%,12.5%and 2.0%, respectively) and controls (88.0%,12.0% and 0.0%,respectively) also had no significant difference (P>0.05). Compared with the C/C genotype, the C/G +G/G genotypes could not increase the risk of developing CRC, the odds ratio was 1.240 (95%CI=0.694~2.217). When stratified for smoking and drinking status, no significant difference in genotype and allele distributions was found between patients and control groups in ST13 rs138344C/G (P>0.05).Conclusions:1 The ST13 rs5758098A/G SNP was associated with the risk of developing CRC. The subjects, particularly non-smokers or non-drinkers, carrying A/G and G/G genotypes could be associated with the increased risk of developing CRC.2 The ST13 rs138335G/C SNP might not be related to the risk of CRC de- velopment.3 There was no significant association between the ST13 rs138344C/G SNP and the risk of developing CRC.