Jun-Ling Ma

Peking University Cancer Hospital, Peping, Beijing, China

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Publications (41)210.68 Total impact

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    ABSTRACT: To investigate the role of cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) in the process of Helicobacter pylori-induced gastric carcinogenesis, a prospective study based on an intervention trial was conducted in Linqu County, China. A total of 1401 subjects with histopathologic diagnosis were investigated at baseline, among those, 919 completed subsequent interventions (anti-H.pylori and/or celecoxib treatment). Expressions of COX-2 and Ki-67 were assessed by immunohistochemistry, and PGE2 levels were measured by enzyme immunoassay before and after interventions, respectively. We found a grade–response relationship between COX-2 expression level and risk of advanced gastric lesions at baseline. Stratified analysis indicated an additive interaction between COX-2 expression and H.pylori infection on the elevated risk of advanced gastric lesions. The odds ratios (ORs) for both factors combined were 9.31 [95% confidence interval (CI): 4.13–20.95] for chronic atrophic gastritis, 16.26 (95% CI: 7.29–36.24) for intestinal metaplasia and 21.13 (95% CI: 7.87–56.75) for dysplasia, respectively. After interventions, COX-2 expression and Ki-67 labeling index (LI) were decreased in anti-H.pylori group (OR: 1.65, 95% CI: 1.36–1.99 for COX-2; OR: 1.78, 95% CI: 1.49–2.12 for Ki-67) or anti-H.pylori followed by celecoxib group (OR: 1.41, 95% CI: 1.17–1.70 for COX-2; OR: 1.63, 95% CI: 1.37–1.94 for Ki-67). PGE2 levels were decreased in all treatment groups. Furthermore, the regression of gastric lesions was associated with the decrease of COX-2 expression or Ki-67 LI after interventions. Our findings indicate that H.pylori-induced COX-2/PGE2 pathways play an important role on the progression of precancerous gastric lesions in a Chinese population.
    No preview · Article · Oct 2015 · Carcinogenesis
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    ABSTRACT: Helicobacter pylori (H. pylori) infection and cytokine-mediated inflammatory responses play important roles in gastric cancer (GC) pathogenesis. To investigate an association between genetic polymorphisms in interleukin (IL)-1β, IL-4R, IL-8, IL-10, IL-16, IL-18RAP, IL-22, and IL-32 and risks of GC and its precursors, a population-based study was conducted in Linqu County. Genotypes were determined by Sequenom MassARRAY platform in 132 GC cases and 1198 subjects with gastric lesions. The H. pylori status was determined by (13)C-urea breath test ((13)C-UBT) or enzyme-linked immunosorbent assay (ELISA). Among 11 candidate single nucleotide polymorphisms (SNPs), subjects carrying IL-18RAP rs917997 AA genotype were associated with risk of GC [adjusted odds ratio (OR) = 1.83, 95 % confidence interval (CI) 1.14-2.92] or chronic atrophic gastritis (CAG; OR = 1.55, 95 % CI 1.07-2.24). The risk of GC was also increased in subjects carrying IL-32 rs2015620 A allele (AA + AT; OR = 1.92, 95 % CI 1.09-3.39). Moreover, elevated risks of CAG (OR = 2.64, 95 % CI 1.89-3.69), intestinal metaplasia (IM; OR = 5.58, 95 % CI 3.86-8.05), and dysplasia (DYS; OR = 1.64, 95 % CI 1.18-2.26) were observed in subjects with IL-22 rs1179251 CC genotype. Stratified analysis indicated that risks of GC and its precursors were elevated in subjects with IL-32 rs2015620 A allele (AA + AT) or IL-22 rs1179251 CC genotype and H. pylori infection, and significant interactions between these two SNPs and H. pylori infection were found. These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions. Genetic polymorphisms of interleukins may play crucial roles in H. pylori-induced gastric carcinogenesis.
    Full-text · Article · Sep 2015 · Tumor Biology
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    ABSTRACT: To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. A total of 184 786 residents aged 25-54 years were enrolled in this trial and received (13)C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. The prevalence of H. pylori in trial participants was 57.6%. A total of 94 101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baseline-value of (13)C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all Ptrend<0.001). However, a dose-response relationship between failure rate and smoking or drinking index was found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. ChiCTR-TRC-10000979 in accordance with WHO ICTRP requirements. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · May 2015 · Gut
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    ABSTRACT: Background Genetic variants of nucleotide-binding oligomerization domain-containing protein (NOD) may influence the outcome of Helicobacter pylori ( H . pylori ) infection and gastric carcinogenesis. To explore genetic variants of NOD1 and NOD2 in association with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, China. Methods TagSNPs of NOD1 and NOD2 were genotyped by Sequenom MASS array in 132 GCs, and 1,198 subjects with precancerous gastric lesions, and were correlated with evolution of gastric lesions in 766 subjects with follow-up data. Results Among seven tagSNPs, NOD1 rs2709800 and NOD2 rs718226 were associated with gastric lesions. NOD1 rs2709800 TG genoty
    No preview · Article · May 2015 · PLoS ONE
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    ABSTRACT: Genetic polymorphisms of Toll-like receptor (TLR) 1 and 10 may influence Helicobacter pylori (H. pylori) susceptibility. To evaluate associations between TLR1 and 10 polymorphisms, H. pylori infection, and precancerous gastric lesions, a population-based study was conducted in a high-risk Chinese population. Three single-nucleotide polymorphisms, TLR1 rs4833095, TLR10 rs10004195, and TLR10 rs4129009 were genotyped by TaqMan SNP genotyping assay in 2553 participants with diverse gastric lesions. The status of H. pylori infection was determined by (13)C-urea breath test. TLR1 rs4833095 T and TLR10 rs10004195 T alleles were the minor alleles and showed in linkage disequilibrium (r(2)=0.73) in the Chinese population. A decreased risk of H. pylori infection was observed in subjects with TLR1 rs4833095 CT genotype [adjusted odds ratio (OR)=0.80; 95% confidence interval (CI): 0.66-0.96] or T allele (OR=0.82; 95%CI: 0.69-0.99). Moreover, subjects carrying TLR1 rs4833095 TT genotype were associated with reduced risks of chronic atrophic gastritis (CAG, OR=0.66; 95%CI: 0.45-0.97) and intestinal metaplasia (IM, OR=0.57; 95%CI: 0.36-0.90). The risk of CAG was also decreased in subjects carrying TLR10 rs10004195 T allele (OR=0.75; 95%CI: 0.57-0.99). Furthermore, haplotype analysis indicated that haplotype TT of rs4833095 and rs10004195 had a protective effect on H. pylori infection (OR=0.83; 95%CI: 0.72-0.96) or precancerous gastric lesions (OR=0.78; 95%CI: 0.64-0.96 for CAG, and OR=0.74; 95%CI: 0.57-0.96 for IM). These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori susceptibility and gastric pathogenesis. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Feb 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: Background: Methylation is a common epigenetic modification which may play a crucial role in cancer development. To investigate the association between methylation of COX-2 in blood leukocyte DNA and risk of gastric cancer (GC), a nested case-control study was conducted in Linqu County, Shandong Province, a high risk area of GC in China. Methods: Association between blood leukocyte DNA methylation of COX-2 and risk of GC was investigated in 133 GCs and 285 superficial gastritis (SG)/ chronic atrophic gastritis (CAG). The temporal trend of COX-2 methylation level during GC development was further explored in 74 pre-GC and 95 post-GC samples (including 31 cases with both pre- and post-GC samples). In addition, the association of DNA methylation and risk of progression to GC was evaluated in 74 pre-GC samples and their relevant intestinal metaplasia (IM)/dysplasia (DYS) controls. Methylation level was determined by quantitative methylation-specific PCR (QMSP). Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by unconditional logistic regression analysis. Results: The medians of COX-2 methylation levels were 2.3 % and 2.2 % in GC cases and controls, respectively. No significant association was found between COX-2 methylation and risk of GC (OR, 1.15; 95 % CI: 0.70-1.88). However, the temporal trend analysis showed that COX-2 methylation levels were elevated at 1-4 years ahead of clinical GC diagnosis compared with the year of GC diagnosis (3.0 % vs. 2.2 %, p = 0.01). Further validation in 31 GCs with both pre- and post-GC samples indicated that COX-2 methylation levels were significantly decreased at the year of GC diagnosis compared with pre-GC samples (1.5 % vs. 2.5 %, p = 0.02). No significant association between COX-2 methylation and risk of progression to GC was found in subjects with IM (OR, 0.50; 95 % CI: 0.18-1.42) or DYS (OR, 0.70; 95 % CI: 0.23-2.18). Additionally, we found that elder people had increased risk of COX-2 hypermethylation (OR, 1.55; 95 % CI: 1.02-2.36) and subjects who ever infected with H. pylori had decreased risk of COX-2 hypermethylation (OR, 0.54; 95 % CI: 0.34-0.88). Conclusions: COX-2 methylation exists in blood leukocyte DNA but at a low level. COX-2 methylation levels in blood leukocyte DNA may change during GC development.
    Preview · Article · Aug 2014 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Among 2258 Helicobacter pylori-seropositive subjects randomly assigned to receive one-time H. pylori treatment with amoxicillin-omeprazole or its placebo, we evaluated the 15-year effect of treatment on gastric cancer incidence and mortality in subgroups defined by age, baseline gastric histopathology, and post-treatment infection status. We used conditional logistic and Cox regressions for covariable adjustments in incidence and mortality analyses, respectively. Treatment was associated with a statistically significant decrease in gastric cancer incidence (odds ratio = 0.36; 95% confidence interval [CI] = 0.17 to 0.79) and mortality (hazard ratio = 0.26; 95% CI = 0.09 to 0.79) at ages 55 years and older and a statistically significant decrease in incidence among those with intestinal metaplasia or dysplasia at baseline (odds ratio = 0.56; 95% CI = 0.34 to 0.91). Treatment benefits for incidence and mortality among those with and without post-treatment infection were similar. Thus H. pylori treatment can benefit older members and those with advanced baseline histopathology, and benefits are present even with post-treatment infection, suggesting treatment can benefit an entire population, not just the young or those with mild histopathology.
    No preview · Article · Jul 2014 · JNCI Journal of the National Cancer Institute
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    Full-text · Article · Jun 2014 · JNCI Journal of the National Cancer Institute
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    ABSTRACT: Helicobacter pylori-specific proteins are involved in gastric carcinogenesis. To investigate the seroprevalence of 6 H. pylori-specific antibodies in patients with different gastric histology, and the impact of seropositivities on the evolution of precancerous gastric lesions, a follow-up study was conducted in Linqu County, China. The seropositivities for CagA, VacA, GroEL, UreA, HcpC and gGT were assessed by recomLine analysis in 573 H. pylori positive subjects and correlated with evolution of precancerous gastric lesions. We found the score of H. pylori recomLine test was significantly increased in subjects with chronic atrophic gastritis (CAG, P<0.0001) or intestinal metaplasia (IM, P=0.0125), and CagA was an independent predictor of advanced gastric lesions, adjusted odds ratios (ORs) were 2.54 (95% CI = 1.42-4.55) for IM and 2.38 (95% CI = 1.05-5.37) for dysplasia (DYS). Moreover, seropositivities for CagA and GroEL were identified as independent predictors for progression of gastric lesions in a longitudinal study, and ORs were 2.89 (95% CI = 1.27-6.59) and 2.20 (95% CI = 1.33-3.64), respectively. Furthermore, the risk of progression was more pronounced in subjects with more than 3 positive antigens (Pfor trend trend = 0.0003). This population-based study revealed that seropositivities for CagA and GroEL might be potential markers to identify patients infected with high-risk H. pylori strains which are related to the development of GC in a Chinese high-risk population, and recomLine test might serve as a tool for risk stratification. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · May 2014 · International Journal of Cancer
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    ABSTRACT: 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. 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). 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). 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.
    Full-text · Article · Jul 2013 · Zhonghua zhong liu za zhi [Chinese journal of oncology]
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    ABSTRACT: To evaluate the effects of two gastric cancer screening schemes for early detection of gastric cancer in a high-risk population. 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. 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). 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.
    No preview · Article · May 2013 · Zhonghua zhong liu za zhi [Chinese journal of oncology]
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    ABSTRACT: Background MicroRNAs (miRNAs) have been implicated in various human diseases. Single nucleotide polymorphisms (SNPs) in inflammation-related miRNA may play an important role in Helicobacter pylori (H. pylori)-induced gastric lesions. To evaluate the associations between miRNA SNPs, H. pylori and gastric lesions, a population-based study was conducted in Linqu County, China. Methodology/Principal Findings Based on serum miRNA array conducted in this population, two SNP loci (miR-146a rs2910164: G>C and miR-27a rs895819: T>C) were determined by polymerase chain reaction-restriction fragment length polymorphism in 2,380 participants with diverse gastric lesions. Using participants with superficial gastritis and mild chronic atrophic gastritis as the reference group, we found that rs2910164 CC carriers had a significantly increased risk of intestinal metaplasia [adjusted odds ratio (OR), 1.42; 95% confidence interval (CI), 1.03–1.97] and dysplasia (OR, 1.54; 95% CI, 1.05–2.25) compared to GG carriers, whereas no significant association was observed for rs895819. Stratified analysis by H. pylori infection indicated that rs2910164 C allele was associated with an increased risk of intestinal metaplasia and dysplasia only among individuals infected with H. pylori (CC vs. GG: OR, 1.53; 95% CI, 1.12–2.08, P for trend = 0.004). Participants who simultaneously carried variant alleles and H. pylori infection were more likely to develop intestinal metaplasia and dysplasia, although the interaction between genetic variants and H. pylori infection was not significant (P for interaction = 0.35 for rs2910164 and 0.92 for rs895819). Conclusions/Significance These findings suggest that miR-146a rs2910164 polymorphism may contribute to the evolution of H. pylori-associated gastric lesions in this high-risk population.
    Preview · Article · Apr 2013 · PLoS ONE
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    ABSTRACT: To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC.
    Full-text · Article · Mar 2012 · PLoS ONE
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    ABSTRACT: In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).
    Full-text · Article · Jan 2012 · Journal of the National Cancer Institute
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    ABSTRACT: Genetic polymorphisms of Toll-like receptors (TLR) may influence the outcome of Helicobacter pylori infection and play important roles in gastric carcinogenesis. To screen the genetic variants of TLR2 and TLR5, and evaluate their associations with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, Shandong Province, China. Genetic variants were identified by PCR-based denaturing high-performance liquid chromatography and PCR-restriction fragment length polymorphism analysis in 248 GC cases, 846 subjects with advanced gastric lesions including 350 dysplasia and 496 intestinal metaplasia, and 496 superficial gastritis/mild chronic atrophic gastritis controls. Nine allelic variants each were detected within the promoter and exons of TLR2 and TLR5. Among those, TLR2 c. -196 to -174 del carriers (ins/del+del/del) showed a significantly decreased risk of GC (adjusted OR, 0.66; 95% CI: 0.48-0.90), whereas TLR5 rs5744174 C carriers (TC+CC) had an increased risk of GC (OR, 1.43; 95% CI: 1.03-1.97). Further analysis indicated an elevated risk of GC in subjects with the TLR5 rs5744174 TC+CC genotype and H. pylori infection (OR, 3.35; 95% CI: 2.13-5.26), and a significant interaction between rs5744174 and H. pylori infection was observed (OR, 2.15; 95% CI: 1.12-4.16). These findings suggest that TLR2 c. -196 to -174 ins > del, TLR5 rs5744174 and interaction between rs5744174 and H. pylori infection were associated with the development of GC. TLR2 and TLR5 polymorphisms may play important roles in the process of H. pylori-related gastric carcinogenesis.
    Full-text · Article · Dec 2011 · Cancer Epidemiology Biomarkers & Prevention
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    Wei-Hong Zhang · Lei Zhang · Wei-Feng An · Jun-Ling Ma
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    ABSTRACT: Prehypertension is common in China and is associated with an increased risk of cardiovascular disease. The present study estimated the current prevalence of prehypertension and its association with clustering of other modifiable cardiovascular risk factors (CRFs) among adults in suburban Beijing. A cross-sectional survey of a representative sample of 19 003 suburban adults aged 18 to 76 years was carried out in 2007. Questionnaire data and information on blood pressure, anthropometric characteristics, and laboratory measurements were collected. The age-standardized prevalence of prehypertension was 35.7% (38.2% in men and 31.8% in women) among adults in suburban Beijing. The prevalence of overweight/obesity, diabetes, dyslipidemia, and physical inactivity was higher in participants with prehypertension (26.7%, 4.8%, 34.3%, and 60.4%, respectively) as compared with normotensive participants (15.9%, 2.7%, 20.5%, and 29.1%, respectively), and in participants with hypertension as compared with those with prehypertension. Overall, 85.3%, 49.8%, and 17.8% of prehypertensive men had 1 or more, 2 or more, and 3 or more CRFs (overweight/obesity, diabetes, dyslipidemia, current smoking, and physical inactivity). These proportions were higher than those in normotensive men (81.5%, 45.1%, and 13.4%) and lower than those in men with hypertension (91.7%, 56.4%, 19.2%). Similar results were found when women with prehypertension were compared with women who were normotensive or hypertensive. A high prevalence of prehypertension and clustering of other modifiable CRFs are common among prehypertensive adults in suburban Beijing. More-effective population-based lifestyle modifications are required to prevent progression to hypertension and reduce the increasing burden of cardiovascular disease in China.
    Preview · Article · Sep 2011 · Journal of Epidemiology
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    ABSTRACT: Helicobacter pylori infection and overexpression of cyclo-oxygenase-2 (COX-2) are associated with gastric cancer and its precursors. To evaluate the effect of a selective COX-2 inhibitor alone and combined with H pylori eradication on the evolution of precancerous gastric lesions, a randomised, placebo-controlled trial was conducted in Linqu County, Shandong Province, China. A total of 1024 participants aged 35-64 years with H pylori infection and advanced gastric lesions were randomly assigned in a factorial design to two interventions or placebo: anti-H pylori treatment for 7 days, and a COX-2 inhibitor (celecoxib) for 24 months. The effects of the interventions were evaluated by the regression or progression of advanced gastric lesions. Of the 1024 participants who received anti-H pylori treatment or placebo, 919 completed a subsequent 24-month treatment with celecoxib or placebo. The H pylori eradication rate by per-protocol analysis was 78.2%. Compared with placebo, the proportions of regression of gastric lesions significantly increased in the celecoxib treatment (52.8% vs 41.2%) and anti-H pylori treatment (59.3% vs 41.2%) group, and OR by per-protocol analysis was 1.72 (95% CI 1.07 to 2.76) for celecoxib and 2.19 (95% CI 1.32 to 3.64) for H pylori eradication. No statistically significant effect was found for H pylori eradication followed by celecoxib on the regression of advanced gastric lesions (OR 1.48, 95% CI 0.91 to 2.40). This population-based intervention trial revealed that celecoxib treatment or H pylori eradication alone had beneficial effects on the regression of advanced gastric lesions. No favourable effects were seen for H pylori eradication followed by celecoxib treatment. Trial registration HARECCTR0500053 in accordance with WHO ICTRP requirements.
    No preview · Article · Sep 2011 · Gut
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    ABSTRACT: To explore the relationship between the polymorphisms of Toll-like receptor 2 (TLR2) and TLR9 and the susceptibility to gastric cancer. 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. 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). Our findings indicate that TLR2 rs3804099 is closely associated with susceptibility to gastric cancer.
    No preview · Article · Jul 2011 · Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]
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    ABSTRACT: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of gastric cancer. Our study aimed to investigate the correlation of RUNX3 methylation, expression and the risk of advanced gastric lesions, based on a high-risk population in Linqu County, Shandong Province, China. Methylation status of RUNX3 was determined by methylation-specific polymerase chain reaction, and expression was detected by immunohistochemical analysis in 1113 subjects with different gastric lesions. Results showed that the frequency of RUNX3 methylation was significantly increased in subjects with advanced gastric lesions. The odds ratios (ORs) were 2.09 [95% confidence interval (CI): 1.49-2.94] for intestinal metaplasia (IM), 3.22 (95% CI: 2.33-4.47) for indefinite dysplasia (Ind DYS) and 2.03 (95% CI: 1.23-3.37) for dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. Stratified analysis indicated that the frequency of RUNX3 methylation was higher in subjects with Helicobacter pylori infection (OR, 2.74; 95% CI: 2.00-3.76). Moreover, there was a reverse grade-response relationship between the level of RUNX3 expression and risk of gastric lesions. Among subjects with mild, moderate or heavy expression, the risk was decreased by 41, 59 or 80% for IM (P(trend) < 0.0001); 40, 64 or 74% for Ind DYS (P(trend) < 0.0001) and 28, 59 or 51% for DYS (P(trend) = 0.045), respectively. Furthermore, RUNX3 expression was negatively associated with increased frequency of RUNX3 methylation (OR, 0.76; 95% CI: 0.59-0.98). These findings suggest that RUNX3 may play important roles in the development of advanced gastric lesions.
    Full-text · Article · Dec 2010 · Carcinogenesis
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    ABSTRACT: Objective To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen (PSCA) and the risk of advanced precancerous gastric lesions including intestinal metaplasia(IM) and dysplasia(Dys), a population-based study was conducted in Linqu County, a high-risk area of gastric cancer (GC) in China. Methods The prevalence of gastric lesions including superficial gastritis(SG), chronic atrophic gastritis(CAG), IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression. Results Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM (OR=1.38, 95% CI=1.11–1.71) and Dys (OR=1.75, 95% CI=1.36–2.26), especially for subjects with H.pylori infection (IM: OR=1.34, 95% CI=1.05–1.71; Dys: OR=1.82, 95% CI=1.37–2.42). Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of IM (OR=3.32, 95% CI=2.33–4.71) and Dys (OR=4.58, 95% CI=2.99–7.04). Conclusion This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.
    No preview · Article · Jun 2010 · Chinese Journal of Cancer Research

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1k Citations
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Institutions

  • 2011-2015
    • Peking University Cancer Hospital
      Peping, Beijing, China
  • 2009-2015
    • Peking University
      Peping, Beijing, China
  • 2006-2014
    • Beijing Cancer Hospital
      Peping, Beijing, China
  • 2008
    • Peking University Health Science Center
      Peping, Beijing, China
  • 2002
    • Beijing Union University
      Peping, Beijing, China
  • 2000
    • Beijing Medical University
      • School of Oncology
      Peping, Beijing, China
  • 1999
    • Shandong Academy of Sciences
      Chi-nan-shih, Shandong Sheng, China
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States