[An association study between transforming growth factor-ß1 receptor 2 gene polymorphisms and essential hypertension].

OBJECTIVE: To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-ß1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. METHODS: The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension. RESULTS: The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05). CONCLUSION: SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Promoter polymorphisms of IL2, IL4, and risk of gastric cancer in a high-risk Chinese population.

Interleukin 2 (IL2) is a typical Th1 cytokine, and interleukin 4 (IL4) is an inducible Th2 cytokine. These cytokines are critical mediators of the Th1/Th2 balance and apoptosis potential and involved in the process of inflammation-mediated carcinogenesis in human organs, including the gastrointestinal tract. Therefore, we tested the hypothesis that functional variants in IL2 and IL4 were associated with risk of gastric cancer by genotyping two promoter polymorphisms in IL2 G-330T (rs2069762) and IL4 T-168C (rs2070874) in a case-control study of 1045 patients with incident gastric cancer and 1100 cancer-free controls in a high-risk Han Chinese population. We found that, compared with the IL4 -168TT genotype, heterozygous -168TC and combined -168TC/CC genotypes were associated with a significantly decreased gastric cancer risk [adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67-0.98 for -168TC; OR = 0.83, 95% CI = 0.69-1.00 for -168TC/CC, respectively]. Furthermore, this significant protective effect was more evident for gastric cardia cancer patients (adjusted OR = 0.73, 95% CI = 0.56-0.95 for -168TC/CC vs. -168TT). For IL2 G-330T, subjects carrying GT/TT genotypes also had a significantly reduced risk of gastric cardia cancer (adjusted OR = 0.68, 95% CI = 0.46-0.99), compared with those carrying the GG genotype. Our results indicate that IL4 T-168C and IL2 G-330T promoter polymorphisms may contribute to the etiology of gastric cardia cancer in Chinese populations.

Potentially functional polymorphisms of the vascular endothelial growth factor gene and risk of gastric cancer.

Vascular endothelial growth factor (VEGF), the key mediator of angiogenesis, plays an important role in the development of different kind of tumors, including gastric cancer (GC). The aim of this study is to test the hypothesis that genetic variants of VEGF are associated with risk of GC. We genotyped four potentially functional polymorphisms (-2578C > A, -1498T > C, -634G > C, and +936C > T) of the VEGF gene in a population-based case-control study of 540 GC cases and 561 frequency-matched cancer-free controls in a high risk Chinese population. We found that none of the four polymorphisms or their haplotypes achieved significant difference in their distributions between GC cases and controls. Multiple logistic regression analyses revealed that GC risk was not significantly associated with the variant genotypes of the four VEGF polymorphisms as compared with their wild-type genotypes. In conclusion, our data did not support a significant association between VEGF SNPs and the risk of GC.

[Study on the association between total plasma homocysteine levels, dietary habits and the risk of gastric cancer].

OBJECTIVE: To explore the relationship between total plasma homocysteine (tHcy) levels, dietary habits and susceptibility of gastric cancer (CGC) in Yangzhong and Yixing cities, the two high GC risk areas in Jiangsu province. METHODS: A population-based case-control study was conducted including 391 histologically-confirmed adenocarcinoma GC cases and 608 age and sex frequency-matched cancer-free controls. The plasma tHcy concentration was measured by enzymatic biochemical assay of homocysteine on microtiter plates, using crude lysate containing recombinant methionine 7-lyase. The relationship between different tHcy levels and risk of GC was analyzed and factors as vegetables and fruits intake, smoking and drinking status were also evaluated together with tHey levels on the risk of GC. RESULTS: The average tHcy levels in GC cases were significantly higher than that in controls (P = 0.002). In addition, according to the quartile levels (7.9, 10.1, 13.7 micromol/L) in the controls, the risks of GC had an increase of 67% (adjusted OR = 1.67, 95% CI: 1.12-2.48), 98% (adjusted OR = 1.98, 95% CI: 1.33-2.94) and 112% (adjusted OR = 2.12, 95% CI: 1.44-3.15) compared to the lowest quartile of tHcy (< or = 7.9 micromol/L), respectively while the increasing trend was significantly noticed (chi2 = 15.78, P < 0.001). The increase of vegetables and fruits intake could decrease the risk of GC. Results from crossover analyses indicated that subjects with less vegetables and fruits intake or both smoking drinking together with plasma tHcy >15.0 micromol/L could increase the GC risk, when compared to the effect on GC risk of each factor. CONCLUSION: These findings supported the hypothesis that the high level of plasma tHcy and the badness dietary habits were associated to the increased risk of GC. Further larger scale and genetics involved studies on the environment and genetic factors were needed to confirm our findings.

[Meta-analysis on the relationship between IL8-251 gene polymorphism and gastric cancer].

OBJECTIVE: To evaluate the relationship between IL8-251 gene polymorphisms and gastric cancer. METHODS: Literatures were reviewed and selected based on the criteria for inclusion. The Meta-analysis software, REVMAN 4.2, was applied to check the heterogeneity across the studies and calculating the pooled OR. RESULTS: Total of 2114 cases and 2505 controls from 8 studies for IL8-251 were included. The chi(2) value was 21.48 (P = 0.003), and the pooled OR of (AA + AT) vs. TT was 1.12 (95% CI 0.90 - 1.40). Large heterogeneity was found among the studies. After the sensitivity analysis, the pooled OR of (AA + AT) vs. TT 1.21 (95% CI 1.06 - 1.39). CONCLUSION: IL8-251-A allele might be associated with higher risk of developing gastric cancer.

[Study on the relationship between compositions of hyperuricemia and metabolic syndrome].

OBJECTIVE: To study the relationship between compositions of hyperuricemia and metabolic syndrome among residents aged > or =20 years. METHODS: A stratified cluster sampling was conducted with 7887 dwellers recruited and examinaed. Blood samples were then collected for serum detection. Available data was analyzed using SPSS 13.0. RESULTS: The incidence rates of obesity, hypertension and hyperglycemia for hyperuricemia were 53.4% with OR = 2.568 (95% CI: 2.103-3.137), 38.8% with OR= 2.157 (95% CI: 1.856-2.508) and 21.9% with OR = 1.850 (95% CI: 1.552-2.205) respectively. Along with the increase of uric acid, body mass index changed the most followed by triglyceridemia. The change of hyperglycemia for men and cholesterol for women were not prominent. Conclusion The relationship between compositions of hyperuricemia and metabolic syndrome was close, suggesting that hyperuricemia might serve as one of the compositions of metabolic syndrome and could contribute to the prevention and control of cardiovascular and cerebrovascular diseases.

[Correlations of polymorphisms of TGFB1 and TGFBR2 genes to genetic susceptibility to gastric cancer].

BACKGROUND & OBJECTIVE: Transforming growth factor beta (TGFbeta) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. The concentration of TGFbeta1 in plasma and the expression of TGFbeta receptor II (TGFbetaRII) are correlated to the development of certain tumors, including gastric cancer. This study was to explore the correlations of functional genetic variants in TGFB1 and TGFBR2 genes to the genetic susceptibility to gastric cancer. METHODS: A case-control study was conducted in Yixing City, a high incidence area of gastric cancer. Polymorphisms of TGFB1 C-509T, TGFB1 Leu10Pro, and TGFBR2 G-875A in 256 gastric cancer patients and 303 cancer-free controls, frequency-matched by age and sex, were determined by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were measured by multivariate Logistic regression analysis to evaluate the correlations of the polymorphisms to the susceptibility to gastric cancer. RESULTS: The TGFB1 C-509T and TGFB1 Leu10Pro were in high linkage disequilibrium (D'=0.86). Compared with wild-type homogenous genetypes -509CC and 10 Leu/Leu, variant genetypes -509CT/TT, 10 Leu/Pro, and 10 Pro/Pro decreased the risk of gastric cancer by 49% and 34% (adjusted OR=0.51, 95% CI=0.36-0.74 for -509CT/TT; adjusted OR=0.66, 95% CI=0.45-0.98 for 10 Leu/Pro or 10 Pro/Pro). The risk of gastric cancer was decreased along with the number of variant sites in the TGFB1 C-509T and TGFBR2 G-875A (Chi(2)=15.70,P < 0.001). Stratified analysis showed that the protective effects of the genotypes were obvious in the subjects of no more than 60-year old (OR=0.42, 95% CI=0.23-0.79) and in non-drinkers (OR=0.45, 95% CI=0.27-0.74). CONCLUSION: Genetic variants of TGFB1 and TGFBR2 genes may contribute to the risk of developing gastric cancer in an eastern Chinese population in Yixing city.

Interaction models of CYP1A1, GSTM1 polymorphisms and tobacco smoking in intestinal gastric cancer.

AIM: To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Val variant and glutathione S-transferase (GST) M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS: A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblings-in-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS: The frequency of the CYP1A1 Val variant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 (95% confidence interval (95%CI): 1.2-3.1, P<0.01). It showed a significant type 2 form of interaction model when both CYP1A1 Val variant allele and former tobacco smoking existed (i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYP1A1 variant alone). The interaction index gamma was 2.8, and OR(eg) (95%CI) was 5.0 (1.9-13.4). GSTM1 null genotype and former tobacco smoking were significant in a type 4 interaction model (i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects). The interaction index gamma and OR(eg) (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively. CONCLUSION: Different interaction models of CYP1A1 Val variant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.

[Study on time-series analysis and forecast models on lung cancer incidence in Qidong, 1972 - 2001].

OBJECTIVE: To explore the lung cancer incidence rates from 1972 to 2001 and utilize varieties of models in forecasting trend up to 2010 in the city of Qidong, Jiangsu in order to provide baseline data for its control and prevention. METHODS: Using data from the cancer registry office in Qidong, we tried to reveal the trends of lung cancer incidence by analyzing the time-series on trends extrapolation, exponent smoothness, Box-Jenkins model etc. We also compared the prognostication precision, endow differ power, and established assembled forecast model. RESULTS: Data showed that there had been a rising trend of lung cancer from 1972 to 2001 and would still probably be on the increase in the future. The rate of male and female attained to 70 per 100 000 and 20 per 100 000, predicting that there would be a respective 33 percent and 10 percent increase in 2010. CONCLUSIONS: According to analysis of forecast models, it was right to prognosticate lung cancer incidence from time-series and improve forecast precision through developing combination models. The result of combination seemed close to ARIMA models which suggested that it could serve as a chief way to forecast the incidence of lung cancer.

Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis.

AIM: To assess the associations of human leukocyte antigen (HLA) class II DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date. METHODS: To clarify the impact of HLA class II polymorphisms on viral clearance, we performed a meta-analysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS: Meta-analyses yielded summary estimates-odds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001] and 2.02 [95%CI (1.56, 2.62), P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION: These results support the hypothesis that specific HLA class II alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4(+)T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and well-designed studies are needed to determine the host genetic determinants of HCV infection.

E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population.

AIM: To test the hypothesis that E-cadherin gene (CDH1) C-160A promoter variant genotype is associated with an increased risk for developing gastric cancer. METHODS: In this population-based case-control study of gastric cancer in Jiangsu Province, China, we performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the C-160A polymorphism of CDH1 promoter in 206 non-cardia gastric cancer patients and 261 age- and sex-matched but unrelated cancer-free controls. RESULTS: The frequencies of genotypes CC, CA and AA were 57.8%, 36.4% and 5.8% in gastric cancer cases, respectively, and 58.2%, 34.9% and 6.9% in controls respectively. The distributions of CDH1 genotypes were not significantly different between gastric cancer cases and controls (P = 0.87 for genotype frequency and P = 0.92 for allele frequency). Compared with the CC genotype, the CA and AA genotypes were not associated with an increased risk for non-cardia gastric cancer (adjusted odds ratios (OR) = 1.15, and 95% confidence interval (95% CI) = 0.78-1.72 for CA genotype, and OR = 0.90 and 95% CI = 0.42-2.01 for AA genotype). CONCLUSION: E-cadherin gene C-160A promoter polymorphism may not play a major role in the etiology of non-cardia gastric cancer in Chinese population.

[A community-based case-control study on risk factors of hyperuricemia among residents in the community].

OBJECTIVE: To investigate the risk factors of hyperuricemia among residents aged >/= 20 years. METHODS: A community based case-control study was conducted in 286 patients with 858 controls without hyperuricemia. Available data were analyzed by mono-factorial and multi-factorial logistic regression methods using SPSS 10.0 software. RESULTS: 17 factors related to exposure were identified for hyperuricemia the mono-factorial analysis when; five factors were selected through multiple factoral logistic regression model at P = 0.05 level. The risk factors on hyperuricemia were: hypertriglyceridemia (OR = 3.069), alcohol consumption (OR = 2.032), obesity (OR = 1.802), taste of spicy food (OR = 1.877) and hyperglycemia (OR = 1.622). CONCLUSION: Hyperuricemia is a disease associated with environment and style-life. Changing lifestyle, such as decreasing alcohol consumption and adopting proper structure of diet may prevent or decrease the chance of getting hyperuricemia and gout.

A novel genetic polymorphism of inducible nitric oxide synthase is associated with an increased risk of gastric cancer.

AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H pylori) infection occurs in humans. iNOS Ser(608)Leu allele, a novel genetic polymorphism (C/T) occurring within exon 16 of the iNOS reductase domain, may have a dramatic effect on the enzymatic activity. The aim of this study was to determine whether iNOS C/T polymorphism was associated with increased susceptibility to gastric cancer. METHODS: We conducted a population based case-control study in a high gastric cancer incidence area, Yangzhong, China. Questionnaires from 93 patients with intestinal type gastric cancer (IGC), 50 with gastric cardia cancer (GCC) and 246 healthy controls were obtained between 1997 and 1998, and iNOS genotyping was carried out. Odds ratios (ORs), interaction index (gamma), and 95% confidence intervals for the combined effects of iNOS genotype and H pylori infection, cigarette smoking or alcohol drinking were estimated. RESULTS: The frequency of (CT+TT) genotypes was higher in cases than in control group (24.48% vs 23.17%), but the difference was not statistically significant. After adjusting for age and gender, past cigarette smokers with (CT+TT) genotypes had a significantly increased risk of IGC (OR = 3.62, 95% CI: 1.23-10.64), while past alcohol drinkers with (CT+TT) genotypes had a significantly increased risk of GCC (OR = 3.33, 95% CI: 1.14-9.67). H pylori CagA negative subjects with (CT+TT) genotypes had a significantly increased risk of both IGC and GCC (OR = 2.19 and 3.52, respectively). CONCLUSION: iNOS Ser(608)Leu allele may be a potential determinant of susceptibility to cigarette -alcohol induced gastric cancer, but larger studies are needed to confirm the observations.