Comparison of two gastric cancer screening schemes in a high-risk population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effects of two gastric cancer screening schemes for early detection of gastric cancer in a high-risk population.</p><p><b>METHODS</b>A cluster random sampling method was used to select local residents aged 40-69 years from Linqu County, Shandong Province. "Serum pepsinogen initial screening combined with further endoscopic examination (PG scheme)" and "direct endoscopic examination (endoscopy scheme)" were conducted. The associations between screening schemes and detection rates of gastric cancer, and early gastric cancer/high-grade intraepithelial neoplasia were evaluated by unconditional logistic regression analysis.</p><p><b>RESULTS</b>Overall, 3654 and 2290 participants completed PG and endoscopy schemes, respectively. A total of 11 (0.30%) cases of gastric cancer and 10 (0.27%) cases of high-grade intraepithelial neoplasia were detected by PG scheme, of which 7 (0.19%) cases were early gastric cancer. While, 19 (0.83%) cases of gastric cancer and 10 (0.44%) cases of high-grade intraepithelial neoplasia were detected by endoscopy scheme, with 12 (0.52%) cases of early gastric cancer. Compared with the PG scheme, the endoscopy scheme had a significantly higher detection rates of gastric cancer (OR = 2.83, 95%CI 1.34-5.98), and early gastric cancer/high-grade intraepithelial neoplasia (OR = 2.12, 95%CI 1.12-4.02).</p><p><b>CONCLUSIONS</b>The endoscopy scheme is more effective in the detection of gastric cancer in a high-risk population, particularly for early gastric cancer/high-grade intraepithelial neoplasia than the PG scheme.</p>

Serological assessment of Helicobacter pylori-specific antibodies and their association with gastric lesions in a high-risk population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the distributions of six Helicobacter pylori (Hp)-specific antibodies in a high-risk population of gastric cancer (GC) and explore the relationship between Hp virulence factors and precancerous gastric lesions.</p><p><b>METHODS</b>Based on the two intervention trials conducted in Linqu County, the seropositivities for CagA, VacA, GroEL, UreA, HcpC and GGT were assessed by recombinant immunoassay (recomLine) in 623 participants with H. pylori infection determined by (13)C-urea breath test ((13)C-UBT) and/or enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>In a total of 623 participants were detected by recomLine analysis, of which 594 were Hp-positive. The seropositivities rates of CagA, VacA, GroEL, UreA, HcpC and GGT were 84.0%, 38.2%, 66.7%, 17.7%, 58.8% and 42.8%, respectively. A total of 523 participants were determined as type I infection of Hp, accounting for 88.1%. Compared with superficial gastritis (SG), the infection rate of Hp type I was higher in the chronic atrophic gastritis (CAG) (P = 0.001).</p><p><b>CONCLUSIONS</b>The results of this population-based study suggest that the virulence factors of Hp may be related to the development of GC in a Chinese high-risk population. The recomLine analysis may serve as a tool for identification of Hp strains and prediction of high-risk population of GC.</p>

The correlation between polymorphisms of Toll-like receptor 2 and Toll-like receptor 9 and susceptibility to gastric cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the polymorphisms of Toll-like receptor 2 (TLR2) and TLR9 and the susceptibility to gastric cancer.</p><p><b>METHODS</b>A population-based case-control study was conducted at Linqu county, Shandong province, China, including a total of 248 cases of gastric cancer. Another total of 496 age and sex-matched controls were randomly selected from the same cohorts. TLR2 rs3804099 and TLR9 rs187084 were detected by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (ORs) and 95% confidence interval (CI) were computed from logistic regression models after adjusting for age, sex, Helicobacter pylori (H. pylori) infection and smoking status.</p><p><b>RESULTS</b>The frequencies of TT, TC and CC genotype on TLR2 rs3804099 in control group were 43.5% (216/496), 46.6% (231/496) and 9.9% (49/496), respectively; whereas those in case group were 53.2% (132/248), 39.9% (99/248) and 6.9% (17/248), respectively. Significant differences in the frequencies of TLR2 rs3804099 were found between case and control groups (χ(2) = 6.665, P = 0.036). It was found that compared with the TT genotype, TC + CC genotype carriers obviously less susceptible to gastric cancer (OR = 0.68, 95%CI: 0.50 - 0.93). Joint effects analysis indicated that the TLR2 rs3804099 TT genotype carriers and H.pylori infectors had higher susceptibility to gastric cancer(OR = 3.42, 95%CI: 2.16 - 5.42), compared with TC + CC genotype carriers and non-H.pylori infection group. The frequencies of TT, TC and CC genotype on TLR9 rs187084 in control group were 33.3% (165/496), 49.0% (243/496) and 17.7% (88/496), respectively; whereas those in case group were 35.9% (89/248), 50.0% (124/248) and 14.1% (35/248), respectively. No significant association with gastric cancer was observed for TLR9 rs187084 polymorphism (χ(2) = 1.684, P = 0.431).</p><p><b>CONCLUSION</b>Our findings indicate that TLR2 rs3804099 is closely associated with susceptibility to gastric cancer.</p>

Quantification of cyclooxygenase-2 methylation in gastric mucosa by denaturing high performance liquid chromatography assay / 中华预防医学杂志

<p><b>OBJECTIVE</b>To setup a quantitative assay for detection of cyclooxygenase-2 (COX-2) methylation in human gastric mucosa samples.</p><p><b>METHODS</b>A standard analysis system was established by denaturing high performance liquid chromatography (DHPLC) under the condition of 55 degrees C oven temperature and a linear acetonitrile gradient (4.0/min). While, a total of 10 cases of gastric biopsy samples were detected for methylation status of COX-2.</p><p><b>RESULTS</b>The complete methylated human promyelocytic leukemia cells (HL-60) and unmethylated gastric cancer cell line (MGC803) were used as positive and negative control. The proportion of the methylated copies of COX-2 was calculated according to the peak heights of methylated (M) and unmethylated (U) COX-2 in same PCR amplicon. The formula was Y = 1.0608 x M/(M + U), R(2) = 0.9894. Among 10 biopsy samples, the proportions of methylated copies of COX-2 in 2 cases of dysplasia were higher than superficial gastritis and chronic atrophy gastritis (24.5%, 18.4% vs 7.6%, 9.6%).</p><p><b>CONCLUSION</b>The methylation of COX-2 promoter CpG islands can be detected in human gastric mucosa samples by quantitative DHPLC assay, which could be used in the population-based study of precancerous gastric lesions.</p>

Role of KAI1 gene expression and loss of heterozygosity of KAI1 in metastatic potential and prognosis of pancreatic cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of KAI1 gene expression and loss of heterozygosity (LOH) of KAI1 in metastatic potential and prognosis of pancreatic cancer.</p><p><b>METHODS</b>The expression of KAI1 gene was studied by immunohistochemistry for CD82 on paraffin-embedded tumor tissues. The LOH of KAI1 gene was detected by microdissection, polymerase chain reaction (PCR) and denaturing high performance liquid chromatography (DHPLC).</p><p><b>RESULTS</b>The positivity rate of CD82 in primary pancreatic cancer was 76% (47/62). CD82 expression was significantly higher (P < 0.01) in earlier tumor stages (I and II), as compared to the advanced tumor stages ( III and IV) in which nodal or distant metastases were present. The expression rate of CD82 in patients who survived for more than one year was higher than that in patients who survived for less than one year (P < 0.05). The percentage of LOH at D11S1344 and D11S1326 loci was 17%.</p><p><b>CONCLUSIONS</b>The abnormal expression of CD82 which participates in malignant progression of pancreatic cancer is probably associated with LOH of KAI1 gene. Detection of CD82 expression and LOH of KAI1 gene may carry potential clinical significance in evaluating the metastatic potential and prognosis of pancreatic cancer.</p>

Association between promoter methylation of cyclooxygenase-2 and expression, and precancerous gastric lesions in a high-risk population / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between cyclooxygenase-2 (COX-2) methylation and expression, and precancerous gastric lesions.</p><p><b>METHODS</b>Methylation status of COX-2 was evaluated by quantitative denaturing high performance liquid chromatography (DHPLC) in 1201 subjects with different gastric lesions. COX-2 expression was assessed by immunohistochemistry and Helicobacter pylori (H pylori) infection status was determined by 13C-urea breath test (13 C-UBT).</p><p><b>RESULTS</b>The percent of COX-2 methylation was increased steadily with the severity of gastric lesions, showing 10.6% of which with superficial gastritis/chronic atrophic gastritis (SG/CAG), 11.8% with intestinal metaplasia (IM) and 13.8% with indefinite dysplasia/dysplasia (Ind DYS/DYS) (chi2 = 8.312, P = 0.016). Stratified analysis indicated that the percents of COX-2 methylation in subjects with H pylori negative still increased with the severity of gastric lesions,of 8.8% in SG/CAG, 10.6% in IM and 14.1% in Ind DYS/DYS (chi2 = 6.629, P= 0.036). Moreover,the methylated proportion of COX-2 was negatively associated with the expression in gastric lesions, from 13.3% with mild expression to 7.6% with strong expression (chi2 = 10.400, P = 0.015).</p><p><b>CONCLUSION</b>Our findings indicated that COX-2 methylation was significantly associated with precancerous gastric lesions and H pylori infection, suggesting that promoter methylation of COX-2 might play an important role in the progression of gastric lesions.</p>

Protein profiles of serum in gastric cancer at a high-risk area by SELDI-TOF mass spectrometry / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the specific and sensitive biomarkers for gastric cancer detection, a surface-enhanced laser desorption and ionization protein chip mass spectrometry (SELDI-TOF-MS) was used to generate protein profiles of serum in gastric cancer at a high-risk area.</p><p><b>METHODS</b>A total of 36 gastric cancer cases and 46 subjects with superficial gastritis were selected from Linqu county, Shandong province, a high-risk area of gastric cancer. Serum samples were collected and Q10 protein chips were used to detect the serum proteomic patterns, and the sensitivity and specificity were assessed.</p><p><b>RESULTS</b>For the comparison of the gastric cancer group (26 out of 36 gastric cancer cases) versus superficial gastritis group (37 out of 46 subjects), the 6 most discriminating peaks (m/z 8587, 6945, 8243, 3899, 7035, and 9943) were identified by the ProteinChip Data Analysis System (ZUCIPDAS). The sensitivity and specificity of this pattern were 88.5% and 97.3%, respectively. A total of 19 subjects (10 gastric cancer cases and 9 superficial gastritis subjects) was selected to test the accuracy of this pattern by using blind method, and the sensitivity and specificity were 80.0% and 88.9% ,respectively.</p><p><b>CONCLUSION</b>Our findings suggest that SELDI profiling of serum might be a potential for gastric cancer detection and screening in high-risk population.</p>

The associations of serum gastrin level with Helicobacter pylori infection / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the associations of serum gastrin-17 (G-17) concentration with helicobacter pylori (Hp) infection.</p><p><b>METHODS</b>A (13)C-urea breath and ELISA test to determine the Helicobacter pylori status and to detect the serum gastrin concentration was conducted in 242 villagers in Linqu of Shandong Province, a high gastric cancer prevalence area in China.</p><p><b>RESULTS</b>Of 242 subjects, 65 of 111 were found Hp-positive in males (58.56%), compared with 65 of 131 in females (49.62%) (chi(2) = 1.932, P = 0.165). The statistical difference was not observed among different age groups (chi(2) = 4.185, P = 0.123). The average level of G-17 among 242 subjects was (24.43 +/- 25.46) pmol/L and it was statistically higher in females (29.87 +/- 28.18) pmol/L than that in males (18.01 +/- 20.11) pmol/L (Z = -3.618, P < 0.001). However, there was no statistical difference found among age groups (chi(2) = 1.948, P = 0.378). The G-17 level in Hp-negative group (35.50 +/- 30.92) pmol/L was observed significantly higher than in Hp-positive group (14.90 +/- 13.79) pmol/L (Z = 5.368, P = 0.0001).</p><p><b>CONCLUSION</b>The G-17 concentration was found higher in Hp-negative subjects than in Hp-positive subjects, and higher in female than in male, but no difference was found among age groups.</p>

Feasibility of HLA-DRB1 matching by using DHPLC / 中国实验血液学杂志

To study feasibility of HLA-DRB1 matching by using denatured high performance liquid chromatography (DHPLC), 20 pairs of DNA samples from donors and recipients of hematopoietic cell transplantation (HCT) for DRB1 matching and 2 pairs of samples from donors and recipient of HCT for DRB1 mismatching were studied by DHPLC and PCR-SSP. After being amplified and annealed slowly to produce heteroduplex, PCR products for exon 2 of DRB1 were detected by DHPLC to find matched or mismatched peaks in chromatogram. The results showed that DHPLC and PCR-SSP were consistant with matched or mismatched HLA-DRB1 typing. The results of DHPLC and PCR-SSP for matching were compared by using kappa test (kappa = 0.776, P = 0.00), which suggested DHPLC for HLA-DRB1 matching was in agreement with PCR-SSP. In conclusion, DHPLC for HLA-DRB1 matching is economic and convenient, moreover, will not be affected by unknown genes in HLA-DRB1 locus.

First report on assessment of the status of engraftment after allogeneic hematopoietic stem cell transplantation by using denaturing high-performance liquid chromatography / 中国实验血液学杂志

Monitoring engraftment of donor cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is supposed to be important for the early diagnosis of graft failure or relapse of malignancy. Several techniques have been reported for this purpose. PCR-based assays analyzing polymorphic short tandem repeats (STR) as markers are attractive because they are sensitive and can be performed rapidly. The intent of this study was to test a novel approach for assessment of donor engraftment using denaturing high-performance liquid chromatography (DHPLC) combined with STR-PCR. The feasibility of this assay and the accuracy of semi-quantitative results were tested in-vitro by using serial DNA mixtures from unrelated individuals. The results showed that dilution experiments of the mock chimerism sample revealed a clear correlation between the percentage of donor or recipient DNA and the proportion of allele peak areas, with the limit of detection for a minor DNA percentage being 5%. Discrimination between donor and recipient was possible in all patients analyzed (n = 51) except for 5 patients whose pre-transplant samples were not available and identical twins in one case. STR results were the same as values obtained by capillary electrophoresis combined with fluorescence labeling multiply PCR. Results were also compared with data obtained with FISH analysis in a subgroup of patients receiving grafts from sex-mismatched donors or with PCR-detectable disease-specific gene products analysis. The results of the microsatellite analysis correlated well with the corresponding clinical findings. Full donor chimerism (FDC) were detected in all patients; decreasing values of donor chimerism were detected concomitantly with the appearance of relapse of disease in 3 patients. Samples from eight patients receiving HLA mismatched-haploidentical transplants from related donors together with cord blood transplants from unrelated donors were analyzed by this method. The results showed all 8 patients achieved FDC derived from related donors. It is concluded that this novel approach allows a rapid, sensitive, economical, auto-mated and non-isotopic STR-PCR testing, thus provides a reliable alternative for assessment of the status of engraftment after allo-HSCT.

Relation between single nucleotide polymorphism in estrogen-metabolizing genes COMT, CYP17 and breast cancer risk among Chinese women / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women.</p><p><b>METHODS</b>COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR-based restriction fragment length polymorphism analysis in 250 breast cancer patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression.</p><p><b>RESULTS</b>COMT Met/Met genotype was found in 10.4% of breast cancer patients, which was significantly higher (P = 0.03) than that in controls (5.2%). Women with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR 2.1, 95% CI 1.1 - 4.5) compared with those with Val/Val or Val/Met genotypes. Stratified analysis showed that the elevated risk of breast cancer, associating with the COMT Met/Met genotype, was evident only among premenopausal women (adjusted OR 4.1, 95% CI 1.2 - 17.3) but not among postmenopausal women (adjusted OR 1.3, 95% CI 0.5 - 3.5). There was no significant difference in the distribution of CYP17 genotypes between breast cancer patients and the control subjects (P = 0.83).</p><p><b>CONCLUSION</b>The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.</p>