Mining of susceptible genes of colon cancer based on GEO / 预防医学

Objective To screen the key genes of colon cancer and to explore the pathogenesis of colon cancer. Methods The expression data were searched from Gene Expression Omnibus (GEO) and the differentially expressed genes were selected by GEO2R. The differentially expressed genes were analyzed by gene ontology (GO) , KEGG pathway and protein-protein interaction networks. Results A total of 324 differentially expressed genes including 61 upregulated genes and 263 downregulated genes were found in more than three GEO series. An analysis of differentially expressed gene pathways revealed that bile secretion, drug metabolism, cytochrome P450, and chemical carcinogenesis were involved in the pathogenesis of colon cancer. Thus 9 key genes were identified, including BMP2, CXCL1, CXCL12, CXCL2, GCG, IL8, MMP1, PHLPP2 and PYY. Conclusion The key genes could be screened by bioinformatics effectively, which might provide the basis for further experimental study.

Comparison of serological detection effects of ELISA using rTpN17 or rTpN47 of Treponema pallidum as antigen with that of TPHA and TRUST / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To clone tpn17 and tpn47 genes of Treponema pallidum and then construct their prokaryotic expression systems,to establish ELISAs based on rTpN17 and rTpN47 as antigens and to evaluate the sensitivity and specificity of the ELISAs for detection of serological diagnosis of syphilis.</p><p><b>METHODS</b>The whole length of tpn17 and tpn47 genes was amplified by PCR and then their prokaryotic expression systems were constructed. SDS-PAGE was used to measure the expression of the target recombinant proteins rTpN17 and rTpN47. Ni-NTA affinity chromatography was applied to extract rTpN17 and rTpN47, while Western blot was performed to determine the specific immunoreactivity of rTpN17 and rTpN47. By using rTpN17 and rTpN47 as the coated antigen, respectively, ELISAs (rTpN17-ELISA and rTpN47-ELISA) were established to detect serum samples from 200 healthy individuals, 25 RA patients, 17 SLE patients and 211 syphilis patients. The detection effects of the ELISAs were compared to those of TRUST and TPHA.</p><p><b>RESULT</b>The sequence similarity of the cloned tpn17 and tpn47 genes was 100 % compared with the corresponding sequences in GenBank. The expression outputs of rTpN17 and rTpN47 were approximately 37.2 % and 26.8 % of the total bacterial proteins, respectively. Both the extracted rTpN17 and rTpN47 could take place remarkable conjugation reactions to the sera with positive antibody against Treponema pallidum.The positive detection rate of TPHA (99.1%) was the highest (P<0.001). The positive detection rates of rTpN17-ELISA (85.3 %) and rTpN47-ELISA (84.3 %) were similar (P>0.05). The positive detection rates of TRUST (72.5 %) was lower than that of rTpN17-ELISA (P=0.001) but similar to that of rTpN47-ELISA (P=0.014). The detection results of all the serum samples from healthy individuals, RA patients and SLE patients were negative, whereas 7.1 % (3/42) of the samples from RA or SLE patients were positive.</p><p><b>CONCLUSION</b>rTpN17 and rTpN47 are still maintaining their original immunoreactivity. The ELISAs using rTpN17 or rTpN47 as the antigen are rapid, simple and convenient, higher sensitivity and specificity methods for serological screening and detection of syphilis.</p>

Study on the application of classification tree model in screening the risk factors of malignant tumor / 中华流行病学杂志

<p><b>OBJECTIVE</b>To introduce the partitioning algorithm of classification tree model, and to explore the value of this data mining technique applied in data analysis of multifactorial diseases as malignant tumors.</p><p><b>METHODS</b>Data was analyzed from a survey that conducted on 84 breast cancer patients and 273 cancer-free controls selected randomly in Jiashan county. The classification tree model was constructed using Exhaustive CHAID method and evaluated by the Risk statistics and the area under the ROC curve.</p><p><b>RESULTS</b>9 out of 105 effect risks factors were selected, in which career was the most important factor indicating that workers, teachers and retirees suffered much more risks than others. Nevertheless, the number of pregnancies, breast examination, reasons for menopause, age at menarche, intake of shrimp, crab, kipper, kelp and laver etc were also risk factors on breast cancer. However, physical exercise played different roles on different people. The Risk statistics of model was 0.174, and the area under the ROC curve was 0.872 which was significantly different from 0.5, suggesting that the classification tree model fit the actuality very well.</p><p><b>CONCLUSION</b>The classification tree model could screen out the major affecting factors quickly and effectively and could also identify the cutting-points for continuous and ordinal variables, as well as revealing the complex interaction among the factors at many levels. This model might become a powerful tool to explore the complexities of the risks on diseases.</p>

A case-control study on the association between the genetic polymorphism of sulfotransferase 1A1, diet and susceptibility of colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between sulfotransferase 1Al polymorphism, diet and colorectal cancer susceptibility.</p><p><b>METHODS</b>A case-control study of 140 cancers and 343 health controls was conducted to investigate the role of sulfotransferase 1A1 polymorphism and meat consumption in colorectal carcinogenesis. Genotypes of sulfotransferase 1A1 polymorphism were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).</p><p><b>RESULTS</b>There was no significant difference in allele frequency of SULT1A1 between the control and cancer patient populations. After adjustment for age, sex, smoking and history of diseases, red meat and well-done meat intake showed no significant association with colorectal cancer. Consumption of red meat more than 5 kg per year combined with SULT1Al slow sulfation (Arg/His and His/His) had a statistically significant association with the risk of rectal cancer ( OR = 3.78; 95% CI: 1.08 - 13. 20) compared to that consumed red meat less than 5 kg per year with fast sulfation (Arg/Arg).</p><p><b>CONCLUSION</b>This study suggests that SULT1A1 slow sulfation combined with higher intake of red meat may be associated with an elevated risk of rectal cancer.</p>

Association between genetic polymorphisms of metabolic enzymes and susceptibility of colorectal cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk.</p><p><b>METHODS</b>A case-control study of 140 patients with cancers and 343 health controls was conducted to investigate the role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case-control study and case-only study. Genotypes of four genes polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.</p><p><b>RESULTS</b>The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254-0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no significant association with the increased risk of colorectal cancer while the mutant variants of UGT1A7 might increase the risk of colorectal cancer significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015-6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7.</p><p><b>CONCLUSION</b>This study suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of colorectal cancer.</p>

Association between genetic polymorphisms in folate metabolic enzyme genes and colorectal cancer: a nested case-control study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the interrelationship of genetic polymorphisms in folate metabolic enzymes (MTHFRC677T, MTHFRA1298C, MTRA2756G and MTRRA66G) and their combinative effects with colorectal cancer (CRC).</p><p><b>METHODS</b>A nested case-control study was designed and carried out. 140 CRC patients and 343 control subjects were included in this study. Polymorphisms of folate metabolic enzyme genes were genotyped by PCR-restriction fragment length polymorphism method. Risk of CRC was estimated by unconditional logistic model, and P value for interaction was calculated by likelihood test.</p><p><b>RESULTS</b>The allele of MTR2756G showed a positive association with CRC (OR = 2.04, 95% CI = 1.22 - 3.40). Those with MTHFR1298AA and MTR 2756AG/GG genotypes had an elevated risk with CRC (OR = 2.57, 95% CI, 1.42 -4.65), and their combinative effect showed a significant association with CRC (P = 0.04).</p><p><b>CONCLUSION</b>MTR2756G allele may be a risk factor of CRC, and interaction may exsit between polymorphisms of MTHFRA1298C and MTRA2756G. Further studies with larger sample and in different ethnic groups are needed.</p>

A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC).</p><p><b>METHODS</b>Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls.</p><p><b>RESULTS</b>The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10).</p><p><b>CONCLUSION</b>CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.</p>

Glutathione S-transferase M1 polymorphism and the risk on colorectal cancer: a multilevel meta regression / 中华流行病学杂志

<p><b>OBJECTIVE</b>In order to investigate the relationship between Glutathione S-transferase M1 (GSTM1) status and the risk on colorectal cancer as well as to detect the related factors to this association.</p><p><b>METHODS</b>A pooled analysis of multilevel Meta-regression was performed to estimate GSTM1 deficiency associated with the risks of colorectal cancer. Then subgroup Meta-regression was undertaken to evaluate the possible relationship between heterogeneity and the related characteristics.</p><p><b>RESULTS</b>The overall pooled odds ratios of colorectal cancer risk associated with GSTM1 deficiency was 1.17 (95% CI: 1.08-1.26). Ethnicity, percent of GSTM1 deficiency in population had significant relationships with heterogeneity across the studies (P < 0.05). Results of subgroup Meta-regression showed that GSTM1 deficiency was significantly associated with colorectal cancer risk in ethnic subgroups of Asians, Caucasians and in low level (lower than 50%) of GSTM1 deficiency population (P < 0.05). The respective pooled ORs were 1.14, 1.25 and 1.29.</p><p><b>CONCLUSION</b>GSTM1 deficiency seemed to be a risk factor for colorectal cancer, while interactions on the characteristics of ethnicity, percentage of GSTM1 deficiency in the studied population were related to this association.</p>