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ABSTRACT: There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test.
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search terms of "MTBDRsl" and "tuberculosis" were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and corresponding 95% confidence interval (CI) for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC) curves were produced.
Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI) was 0.874(0.845-0.899), 0.826(0.777-0.869), 0.820(0.772-0.862), 0.444(0.396-0.492), and 0.679(0.652-0.706) for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI) was 0.971(0.961-0.980), 0.995(0.987-0.998), 0.973(0.963-0.981), 0.993(0.985-0.997), and 0.799(0.773-0.823), respectively. The AUC (standard error) were 0.9754(0.0203), 0.9300(0.0598), 0.9885(0.0038), 0.9689(0.0359), and 0.6846(0.0550), respectively.
Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an appropriate choice for kanamycin and ethambutol. The lack of data did not allow for proper evaluation of the test on clinical specimens. Further systematic assessment of diagnostic performance should be carried out on direct clinical samples.
PLoS ONE 01/2013; 8(2):e55292. · 4.09 Impact Factor
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Jianjian Chen,
Lin Miao,
Guangfu Jin,
Chuanli Ren,
Qiao Ke,
Yun Qian,
Meihua Dong,
Huizhang Li,
Qin Zhang,
Yanbing Ding,
Zhigang Yan, Jianming Wang,
Zheng Liu,
Zhibin Hu,
Yaochu Xu,
Guozhong Ji,
Hongbing Shen
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ABSTRACT: The transforming growth factor (TGF)-β is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-β receptor type I (TGFβR1) may be a modifier of cancer risk by constitutively decreasing the TGF-β inhibitory signals during early tumorigenesis and increasing the TGF-β signals in tumor progression. In this study, we hypothesized that genetic variants of TGFBR1 may influence the risk of gastric cancer. We conducted a two-stage case-control study of gastric cancer, including 650 cases and 683 controls in the first stage and 484 cases and 348 controls in the second stage, and genotyped five tagging single nucleotide polymorphisms (SNPs) to represent common variants in the whole TGFBR1 gene. In the first stage, two SNPs rs6478974 and rs10512263 were found to be potentially associated with risk of gastric cancer (P = 3.35 × 10(-3) for rs6478974 AT vs. TT and P = 0.033 for rs10512263 CT vs. TT), which were further confirmed in the second stage with similar effects (P = 0.144 and 0.049, respectively). After combining the two stages, we found that these two SNPs were associated with a significantly increased risk of gastric cancer in dominant models [adjusted odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14-1.63 for rs6478974 AT/AA vs. TT; adjusted OR = 1.26, 95% CI: 1.05-1.50 for rs10512263 CT/CC vs. TT] or additive model (adjusted OR = 1.23, 95% CI: 1.08-1.40 for rs6478974). These findings indicate that TGFBR1 polymorphisms may be implicated with the development of gastric cancer in Han-Chinese population. © 2012 Wiley Periodicals, Inc.
Molecular Carcinogenesis 08/2012; · 3.16 Impact Factor
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ABSTRACT: This study aimed to explore the roles of three common single nucleotide polymorphisms in the X-ray repair cross-complementing group-1 gene (XRCC1) and of life style factors and their possible interactions in the risk of esophageal squamous cell carcinoma (ESCC) in China.
A population-based case-control study of 432 cases and 915 controls was conducted in Yangzhong County, Jiangsu Province, China. Subjects were interviewed by trained interviewers using a structured questionnaire that included questions on demographics and life style. XRCC1 genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay. Unconditional logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations of ESCC with XRCC1 polymorphisms and lifestyle-related factors.
Both the drinking of river water and alcohol intake history were significantly associated [SW1]with an increased risk of ESCC among men with aORs of 4.20 (95% CI: 2.90-6.07) and 2.03 (95% CI: 1.43-2.89), respectively. For women, the corresponding odds ratios were 8.37 (95% CI: 5.09-13.75) for river water drinking and 12.78 (95% CI: 2.69-60.69) for long-term stored rice intake. After the XRCC1 G28152A polymorphism was adjusted for potential confounders, subjects with GA and AA genotypes had an increased risk for ESCC (aOR: 1.21, 95% CI: 0.93-1.56), compared with subjects with a GG genotype, and a positive multiplicative interaction between intake of long-term stored rice and the XRCC1 G28152A polymorphism was observed (P=0.009).
Our findings suggest that both lifestyle-related factors, including drinking river water, long-term stored rice and alcohol intake, and the XRCC1 G28152A polymorphism were possible risk factors for ESCC, and that the XRCC1 G28152A polymorphism modified the effect of long-term stored rice intake on the risk of ESCC among Chinese people.
Biomedical and Environmental Sciences 06/2011; 24(3):268-74. · 1.35 Impact Factor
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ABSTRACT: Folic acid may affect the development of human cancers. However, few studies have evaluated the consumption of diet folate in the prognosis of patients with esophageal squamous cell carcinoma (ESCC).
One hundred and twenty five ESCC patients underwent esophagectomy between January 2005 and March 2006 in the Yangzhong People's Hospital were recruited and followed up. The effects of diet folate, aberrant DNA methylation of selected genes and methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphisms on the prognosis of ESCC were evaluated by using Cox proportional hazard regression models.
Our analysis showed an inverse association between diet folate intake and the risk of death after esophagectomy. The median survival time was 3.06 years for low or moderate folate consumption and over 4.59 years for high folate consumption. After adjusting for potential confounders, the hazard ratios (95% confidence interval) [HRs (95% CI)] were 0.72 (0.36-1.46) for moderate and 0.39 (0.20-0.78) for high folate intake, respectively (P for trend = 0.007). This preventive effect was more evident in patients carrying MTHFR 677CC genotype. No significant relation was observed between aberrant DNA methylation of P16, MGMT and hMLH1 gene, as well as MTHFR C677T genetic polymorphisms and the prognosis of ESCC.
Our research indicated that diet folate intake may have benefits on the prognosis of ESCC after esophagectomy. From a practical viewpoint, the findings of our study help to establish practical intervention and surveillance strategies for managements of ESCC patients and can finally decrease the disease burden.
BMC Cancer 03/2011; 11:91. · 3.01 Impact Factor
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Hanze Zhang,
Guangfu Jin,
Huizhang Li,
Chuanli Ren,
Yanbing Ding,
Qin Zhang,
Bin Deng, Jianming Wang,
Zhibin Hu,
Yaochu Xu,
Hongbing Shen
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ABSTRACT: Two recent genome-wide association studies reported significant associations of genetic variants at 1q22, 10q23 and 20p13 with gastric cancer (GC) risk in Chinese populations. However, these findings have not been confirmed in other independent studies. Here, we performed an independent case-control study in a Chinese population by genotyping three loci (rs4072037A>G at 1q22, rs2274223A>G at 10q23 and rs13042395C>T at 20p13) in 1681 GC cases and 1858 controls. We found that rs4072037 at 1q22 and rs2274223 at 10q23 were significantly associated with risk of GC with per allele odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.63-0.81; P = 2.98 × 10(-7)] and 1.42 (95% CI: 1.27-1.58; P = 9.68 × 10(-10)), respectively. The association was more prominent for rs2274223 in female (OR = 1.86, 95% CI: 1.49-2.32) and gastric cardia adenocarcinoma (GCA) (OR = 1.71, 95% CI: 1.49-1.95). Furthermore, we combined the two single-nucleotide polymorphisms to evaluate the joint effect and found that the GC risk significantly increased with the number of risk allele increasing with a trend P value of 6.66 × 10(-16), and individuals with four risk alleles had a 3.28-fold (95% CI: 1.75-6.13) risk of GC compared with those having no risk alleles. However, no significant association was detected between rs13042395 at 20p13 and GC risk (OR = 1.04, 95% CI: 0.94-1.15; P = 0.452). In conclusion, our results indicate that genetic variants at 1q22 and 10q23 but not 20p13 may serve as candidate markers for GC susceptibility in the Chinese population.
Carcinogenesis 03/2011; 32(6):848-52. · 5.70 Impact Factor
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ABSTRACT: Drug resistance has been a cause of concern for tuberculosis (TB) control in both developed and developing countries. Careful monitoring of the patterns and trends of drug resistance should remain a priority.
Strains were collected from 1824 diagnosed sputum smear positive pulmonary TB patients in Jiangsu province of China and then tested for drug susceptibility against rifampicin, isoniazid, ethambutol and streptomycin. The prevalence and patterns of drug resistance in mycobacterium tuberculosis (MTB) isolates were investigated. Multiple logistic regression analysis was performed to identify the risk factors for multidrug resistant (MDR) bacterial infection. The strength of association was estimated by odds ratio (OR) and 95% confidence interval (95% CI).
The drug susceptibility tests showed that 1077(59.05%) MTB strains were sensitive to all the four antibiotics and the other 747(40.95%) strains were resistant to at least one drug. The proportions of mono-drug resistance were 28.73% for isoniazid, 19.41% for rifampicin, 29.33% for streptomycin, and 13.98% for ethambutol, respectively. The prevalence of MDR-TB was 16.61%, which was significantly different between new cases (7.63%) and those with previous treatment history (33.07%). Geographical variation of drug resistance was observed, where the proportion of MDR-TB among new cases was higher in the central (9.50%) or north part (9.57%) than that in the south area (4.91%) of Jiangsu province. The age of patients was significantly associated with the risk of drug resistance (P < 0.001) and the adjusted OR (95% CI) was 1.88(1.26-2.81) for patients aged 35-44 years when compared with those 65 years or older. Patients with previous treatment history had a more than 5-fold increased risk of MDR-TB (adjusted OR: 6.14, 95% CI: 4.61-8.17), compared with those previously not having been treated.
The high prevalence of drug resistance has been a major challenge for TB control. Prevention and control of drug-resistant TB should be emphasized by the revised DOTS (direct observed therapy, short course) program through prompt case detection, routine and quality-assured drug susceptibility test for patients at high risk of resistance, programmatic treatment with both first and second-line medicines, and systematic treatment observation, with priority for high MDR-TB settings.
BMC Public Health 02/2011; 11:110. · 2.00 Impact Factor
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Hao Shen,
Cheng Lu,
Yue Jiang,
Jinhai Tang,
Wei Chen,
Hanze Zhang,
Qin Zhang, Jianming Wang,
Jie Liang,
Zhibin Hu,
Hongbing Shen
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ABSTRACT: Ultraconserved elements (UCEs) are the most extreme representatives of conserved non-coding sequences. Recent studies have indicated that UCEs are not mutation cold regions and likely to be concerned with cancers, including breast cancer (BC). In this study, we first screened common single-nucleotide polymorphisms (SNPs) (minor allele frequency, MAF > 0.05) in Chinese population located in 481 UCEs sequences and selected seven SNPs (rs17049105, rs13020355, rs2682406, rs2056116, rs11190870, rs9572903, and rs8004379) of uc.51, uc.82, uc.133, uc.140, uc.302, uc.353, and uc.368, respectively. A two-stage case-control study of BC with a total of 1,497 cases and 1,497 controls in Chinese population was conducted to test the hypothesis that these SNPs of UCEs are associated with BC risk. Stage I with 735 cases and 735 controls was designed to discover the risk variants, followed by stage II with 762 cases and 762 controls to validate the significant variants. In stage I, although the genotype distributions of all seven SNPs were not significantly different between BC cases and controls, logistic regression analyses revealed that the variant genotypes of rs8004379 were significantly associated with the increased risk of BC (dominant model: adjusted OR = 1.27, 95% CI = 1.01-1.58, P = 0.039). We then selected two SNPs, rs8004379 A/C and rs2056116 A/G, with lowest P values of the associations into the stage II analysis. However, none of above two SNPs were significantly associated with BC risk in both stage II and pooled set (rs8004379 AC/CC vs. AA: adjusted OR = 0.88, 95% CI = 0.68-1.13 for stage II and adjusted OR = 1.09, 95% CI = 0.92-1.29 for the pooled set; rs2056116 AG/GG vs. AA: adjusted OR = 1.12, 95% CI = 0.87-1.45 for stage II and adjusted OR = 1.11, 95% CI = 0.94-1.31 for the pooled set). These findings did not support a significant association between UCEs SNPs and the risk of BC in Chinese population.
Breast Cancer Research and Treatment 02/2011; 128(3):855-61. · 4.43 Impact Factor
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ABSTRACT: Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population.
The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system.
As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA(rs8087945-rs12456774), haplotypes AG(rs8087945-rs12456774) and GA(rs8087945-rs12456774) were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively.
Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.
BMC Infectious Diseases 01/2011; 11:282. · 3.12 Impact Factor
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Qiao Liu,
Dandan Yang,
Weiguo Xu, Jianming Wang,
Bing LV,
Yan Shao,
Honghuan Song,
Guoli Li,
Haiyan Dong,
Kanglin Wan,
Hua Wang
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ABSTRACT: Globally, China is the second place with high burden of tuberculosis (TB). To explore the characteristics of the pathogens of Mycobacterium tuberculosis (MTB) circulating in this area is helpful for understanding and controlling the spread of the strains. Recent developments in molecular biology have allowed prompt identification and tracking specific strains of MTB spreading through the population.
Spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) were performed in combination to yield specific genetic profiles of 260 MTB strains isolated from 30 counties of Jiangsu province in China between June and July 2010. The spoligotyping results were in comparison to the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Drug susceptibility test (DST) was performed on all strains by proportion method on Lowenstein-Jensen (LJ) culture media.
Based on the spoligotyping method, 246 strains displayed known patterns and 14 were absent in the database. Predominant spoligotypes belonged to the Beijing family (80.4%). By using the 24-loci VNTR typing scheme, 224 different patterns were identified, including 20 clusters and 204 unique patterns. The largest clade comprised 195 strains belonging to the Beijing family. The combination of spoligotyping and 24-loci MIRU-VNTR demonstrated maximal discriminatory power. Furthermore, we observed a significant association between Beijing family strains and drug-resistant phenotypes. The Beijing family strains presented increased risks for developing multi-drug resistant TB, with the OR (95% CI) of 11.07(1.45-84.50).
The present study demonstrated that Beijing family isolates were the most prevalent strains circulating in Jiangsu province of China. The utility of spoligotyping in combination with 24-loci MIRU-VNTR might be a useful tool for epidemiological analysis of MTB transmission.
BMC Infectious Diseases 01/2011; 11:288. · 3.12 Impact Factor
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ABSTRACT: Tuberculosis (TB) patients have difficulty following a long-term treatment regimen. Efforts to improve treatment outcomes require better understanding of adherence as a complex behavioral issue and of the particular barriers to and facilitators of patient adherence.
This study was carried out in Jiangsu Province of China with both quantitative and qualitative approaches. For the quantitative study, 780 sputum-smear positive TB patients consecutively registered since 2006 in 13 counties (districts) were queried with a structured questionnaire. Patients who had missed 10% of their total prescribed doses of TB drugs were deemed as non-adherent. Risks for non-adherence were estimated by computing odds ratios (ORs) and their 95% confidence intervals (95% CIs) using a logistic regression model. We also invited 20 TB patients and 10 local health workers for in-depth interviews. We then used content analysis based on this qualitative study to explore factors associated with non-adherence.
The proportion of non-adherence among 670 patients was 12.2%. Univariate analysis showed that patients, who were illiterate, divorced/widowed, lacked health insurance and were migrants, were more likely to be non-adherent. The crude ORs(95%CIs) were 2.38(1.37-4.13), 2.42(1.30-4.52), 1.89(1.07-3.32) and 1.98(1.03-3.83), respectively. The risk of non-adherence was lower among patients whose treatment was given under direct observation by village doctors or regular home visits by health workers, with ORs (95% CIs) of 0.19(0.10-0.36) and 0.23(0.10-0.51), respectively. In multivariate analysis, factors associated with non-adherence included illiteracy (OR: 2.42; 95% CI: 1.25-4.67) and direct observation by village doctors (OR: 0.23; 95% CI: 0.11-0.45). The in-depth interviews indicated that financial burdens and extra medical expenditures, adverse drug reactions, and social stigma were additional potential factors accounted for non-adherence.
More importance should be given to treatment adherence under the current TB control program. Heavy financial burdens, lack of social support, adverse drug reactions and personal factors are associated with non-adherence. Direct observation and regular home visits by health workers appear to reduce the risk of non-adherence. More patient-centered interventions and greater attention to structural barriers are needed to improve treatment adherence.
BMC Health Services Research 09/2009; 9:169. · 1.66 Impact Factor
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ABSTRACT: As a risk factor of tuberculosis (TB), tobacco smoking has increased substantially over the past three decades, especially in developing countries. However, the association between smoking and TB, which has been shown to exist in different studies with different ethnic background, has not yet received sufficient attention in terms of TB care standards and research in China.
An observational study was conducted in two rural areas of China. A total of 613 TB patients frequency matched with 1226 controls were interviewed by using a structured questionnaire. The associations between cigarette smoking and risk of TB were estimated by computing odds ratios (ORs) and 95% confidence intervals (95% CIs) from logistic regression model. Patients' smoking behavior and patterns of smoking cessation were followed after TB diagnosis. Multivariate Cox proportional hazards model was applied to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) in analyzing the risk factors for smoking relapse. The Kaplan-Meier estimate was computed to plot the ability of smoking-free after cessation among different groups, with the Log-rank test being used to compare the difference.
The proportion of cigarette smoking was 54.6% in TB cases, which was significantly higher than that in controls (45.1%) with adjusted OR of 1.93(95% CI: 1.51-2.48). Though 54.9% smokers stopped smoking after being diagnosed with TB, more than 18% relapsed during the follow-up period. The proportion of relapse was higher within 6-9 months (6%) and 12-15 months (11%) after cessation. In the Cox regression estimates adjusted for age and gender, compared with those highly educated and previously treated patients, the hazard ratios of smoking relapse were 3.48(95% CI: 1.28-9.47) for less educated (<6 years) and 4.30(95% CI: 1.01-18.30) for newly treated patients, respectively.
Cigarette smoking is associated with TB in the Chinese. Interventions of smoking cessation are recommended to be included in the current TB control practice.
BMC Public Health 09/2009; 9:292. · 2.00 Impact Factor
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ABSTRACT: To analyse the current status of directly observed therapy (DOT) and completion of treatment of tuberculosis (TB) in two rural areas of China.
Two rural counties with low DOT rates were deliberately selected as study sites. Face-to-face interviews were conducted by trained investigators with a structured questionnaire to investigate the characteristics of patients and the TB service that they had received. The associations between treatment completion and potential factors were estimated by computing odds ratios (ORs), as well as their 95% confidence intervals (CIs), from an unconditional logistic regression model.
Among 601 patients, 2.2% were treated with direct observation by health workers, 6.2% were supervised by family members, and 91.7% were treated with self-administered therapy. The treatment completion rate was found to be significantly associated with sputum smear test and adverse reaction to anti-tuberculosis drugs, but not with direct observation by health workers (OR 1.81, 95% CI 0.23-14.38) or by family members (OR 1.14, 95% CI 0.38-3.41). Frequent home visiting by health workers (!1 visit/month) could help to increase the completion rate (OR 3.15, 95% CI 1.30-7.63).
No significant difference was found in the rate of completion of TB treatment between direct observation and self-supervision groups in two rural areas with lower DOT coverage. How to build a feasible DOT strategy that is accepted by both patients and healthcare providers needs to be considered by policy-makers. Other elements apart from DOT are necessary to ensure a successful TB programme.
Scandinavian Journal of Public Health 04/2009; 37(3):304-9. · 1.39 Impact Factor
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ABSTRACT: Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors.
Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly.
Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores.
TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.
BMC Public Health 11/2008; 8:354. · 2.00 Impact Factor
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Guangfu Jin,
Yimei Deng,
Ruifen Miao,
Zhibin Hu,
Yan Zhou,
Yongfei Tan, Jianming Wang,
Zhaolai Hua,
Weiliang Ding,
Lina Wang,
Wensen Chen,
Jing Shen,
Xinru Wang,
Yaochu Xu,
Hongbing Shen
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ABSTRACT: Transforming growth factor beta1 (TGF-beta1) and its receptor II (TGF-betaRII) are two key components of TGF-beta signaling and play an important role in carcinogenesis. Several functional polymorphisms were identified in TGFB1 and TGFBR2 and associated with elevated serum or plasma level of TGF-beta1 and enhanced transcription activity of TGFBR2. This population-based case-control study was to evaluate the contribution of functional polymorphisms in TGFB1 C-509T, Leu10Pro and TGFBR2 G-875A to the risk of esophageal squamous cell carcinoma (ESCC).
Genotyping was performed using the primer-introduced restriction analysis-PCR assay in 255 ESCC cases and 704 cancer-free controls in a Chinese population.
The variant genotypes (-509CT/TT) of TGFB1 C-509T were associated with a 63% significantly decreased risk of ESCC (adjusted OR = 0.37, 95% CI = 0.27-0.50) compared with -509CC wild-type homozygote. In addition, a moderately decreased risk of ESCC was related to -875GA (adjusted OR = 0.70, 95% CI = 0.49-0.99) but not -875AA genotype (adjusted OR = 1.09, 95% CI = 0.51-2.35) in TGFBR2, compared with -875GG common genotype. Furthermore, subjects carrying variant genotypes either or both of TGFB1 C-509T and TGFBR2 G-875A had a significantly reduced risk of ESCC (adjusted OR = 0.37, 95% CI = 0.26-0.53 for either one variant genotype and adjusted OR = 0.30, 95% CI = 0.19-0.48 for both variant genotypes) in a dose-response manner (chi (trend) (2) = 33.87, P < 0.001) compared with subjects with both wild-type genotypes.
These results are consistent with our previous findings in gastric cancer and support the hypothesis that genetic variants in TGFB1 and TGFBR2 may modulate the risk of ESCC.
Journal of Cancer Research and Clinical Oncology 03/2008; 134(3):345-51. · 2.56 Impact Factor
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ABSTRACT: To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiologic study in China. One hundred and twenty-five histologically confirmed ESCC patients having undergone surgery in the Yangzhong People's Hospital between January 2005 and March 2006 were recruited. The aberrant CpG island hypermethylation of P16, MGMT, and hMLH1 genes could be found in cancer tissues with frequency of about 88.0%, 27.2%, and 3.2%, respectively, and in remote normal-appearing esophageal tissues with frequency of about 36.8%, 11.2%, and 0.0%, respectively. No hypermethylation was found in the normal esophageal tissues from healthy controls. Compared with those patients without lymph node metastasis, MGMT gene showed a higher proportion of hypermethylation in cancer tissues, whereas P16 gene showed a higher proportion of hypermethylation in remote normal-appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues, with odds ratio of 3.34 (95% confidence interval, 1.07-10.39) and 3.83 (95% confidence interval, 1.13-12.94), respectively. This study indicated that the aberrant CpG island hypermethylation of cancer-related genes was associated with ESCC and might be a promising biomarker in diagnosis and prognosis.
Cancer Epidemiology Biomarkers & Prevention 02/2008; 17(1):118-25. · 4.12 Impact Factor
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Guangfu Jin,
Ruifen Miao,
Yimei Deng,
Zhibin Hu,
Yan Zhou,
Yongfei Tan, Jianming Wang,
Zhaolai Hua,
Weiliang Ding,
Lina Wang,
Wensen Chen,
Jing Shen,
Xinru Wang,
Yaochu Xu,
Hongbing Shen
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ABSTRACT: Epidermal growth factor (EGF), a ligand of the EGF receptor, plays a critical role in the development of gastric cancer. Genetic variants in its promoter region may influence transcription activity and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped three EGF promoter polymorphisms (G61A, G-1380A, and A-1744G) in a case-control study of 675 gastric cancer cases and 704 cancer-free controls. We found that the variant genotypes of EGF 61GA/AA were associated with a significantly decreased risk of gastric cancer (OR = 0.77, 95% CI = 0.61-0.95), when compared with wild-type homozygote 61GG. In the combined analysis with all three loci of EGF, subjects carrying one or more variant loci had a significantly decreased risk of gastric cancer in a dose-response manner (adjusted OR = 0.58, 95% CI = 0.42-0.80 for subjects carrying one variant locus and OR = 0.46, 95% CI = 0.32-0.66 for those carrying two to three variant loci, respectively; trend test: chi(2) = 16.14, P < 0.001). Compared with the most common haplotype GGA, haplotypes AGA, GGG and GAA (each containing one variant allele) were associated with 33%, 29% and 34% significantly decreased risk of gastric cancer (adjusted OR = 0.67, 95% CI = 0.55-0.82 for AGA; OR = 0.71, 95% CI = 0.57-0.88 for GGG and OR = 0.66, 95% CI = 0.52-0.84 for GAA, respectively). Our findings indicate that variant genotypes and haplotypes of EGF promoter might play a role in gastric carcinogenesis.
Cancer Science 06/2007; 98(6):864-8. · 3.33 Impact Factor
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Guangfu Jin,
Lina Wang,
Wensen Chen,
Zhibin Hu,
Yan Zhou,
Yongfei Tan, Jianming Wang,
Zhaolai Hua,
Weiliang Ding,
Jing Shen,
Zuofeng Zhang,
Xinru Wang,
Yaochu Xu,
Hongbing Shen
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ABSTRACT: Growing evidence suggests that the transforming growth factor beta (TGF-beta) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGF-beta1 and its receptor TGF-betaRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.82 for -509CT/TT and adjusted OR = 0.67, 95% CI = 0.53-0.85 for -875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI = 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility.
International Journal of Cancer 04/2007; 120(6):1330-5. · 5.44 Impact Factor
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Lina Wang,
Qiao Ke,
Wensen Chen, Jianming Wang,
Yongfei Tan,
Yan Zhou,
Zhaolai Hua,
Weiliang Ding,
Juying Niu,
Jing Shen,
Zuofeng Zhang,
Xinru Wang,
Yaochu Xu,
Hongbing Shen
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ABSTRACT: Accumulative evidence suggests that folate has a protective effect on gastric cancer. The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase (MTHFR).
We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population.
The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for 401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TT genotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls (P < 0.01), and the upper quartile of tHcy (>13.6 micromol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy (<or=8.0 micromol/L; adjusted OR, 1.82; 95% CI, 1.20-2.75).
The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.
Clinical Cancer Research 04/2007; 13(8):2526-32. · 7.74 Impact Factor
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Jing Shen,
Runtian Wang,
Liwei Wang,
Zhaoxi Wang,
Houxun Xing,
Binyan Wang,
Maosen Li,
Zhaolai Hua, Jianming Wang,
Chunhua Guo,
Xinru Wang,
Xiping Xu
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ABSTRACT: To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people.
A community-based case-control study was designed. Ninety-three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty-six controls served as controls.
C-->T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509 I restriction enzyme (we called it C-->T polymorphism). The T allele gene frequency in the control group was 13.21%. No statistically significant difference was found between C-->T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C-->T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C-->T polymorphism occurred.
C-->T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco-related but CagA negative types of intestinal stomach cancer and stomach cardia cancer.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 10/2002; 23(5):374-7.
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Jing Shen,
Runtian Wang,
Zhaoxi Wang,
Houxun Xing,
Liwei Wang,
Bingyan Wang,
Maosen Li,
Zhaolai Hua, Jianming Wang,
Chunhua Guo,
Xinru Wang,
Xiping Xu
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ABSTRACT: To find out the distributive features of some metabolic genes polymorphisms in Han population of south area of China.
Study population was obtained from the controls of a community based case-control study, which included 290 blood relatives (inner control) and 404 non-blood relatives (outer control).
Frequencies of CYP1A1, GSTM1 and GSTT1 polymorphisms had no significant difference among confounding factors, such as sex, living areas, stomach cancer family history and history of tobacco smoking etc. Some controls showed significant difference in age group and alcohol drinking which would be adjusted in analysis of the relationship between polymorphisms and cancers. CYP1A1 Ile/Val and Val/Val genotypes were 33.43% and 5.62% respectively, which were similar to other results from Chinese and Japanese, but higher than those from Caucasians in American, Europe and African-Americans. GSTM1 null allele frequency was 53.48% in our population, which showed difference even among Chinese in different areas. GSTT1 null allele frequency was 45.78%, which was significantly higher than that in Caucasians and African-American.
The frequencies of CYP1A1 Ile/Val, Val/Val and GSTT1 null in Han population in south area of China are significantly higher than those in other races, while the ethnic difference of frequency of GSTM1 null is less.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 09/2002; 19(4):302-7.
