TGFBR1 tagging SNPs and gastric cancer susceptibility: a two-stage case-control study in Chinese population.

The transforming growth factor (TGF)-ß is a potent growth inhibitor primarily responsible for cell growth, differentiation, and apoptosis, and frequently perturbed during development of tumors, including gastric cancer. TGF-ß receptor type I (TGFßR1) may be a modifier of cancer risk by constitutively decreasing the TGF-ß inhibitory signals during early tumorigenesis and increasing the TGF-ß 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.

Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations.

Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent case-control study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] = 0.69, 95% confidence interval [95% CI] = 0.55-0.87) and replication stage (OR = 0.80, 95% CI = 0.68-0.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream of TERT) was significantly associated with a decreased risk of gastric cancer (OR = 0.76, 95% CI = 0.67-0.87, P = 5.35 × 10(-5)). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P = 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.

[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.

A genetic variant in 3'-untranslated region of cyclooxygenases-2 gene is associated with risk of gastric cancer in a Chinese population.

Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis, including inflammation, apoptosis inhibition, immune response suppression, tumor cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers, including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase 2 (PTGS2) gene. We hypothesized that potentially functional polymorphisms in PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we conducted a case-control study with 1681 gastric cancer cases and 1916 control subjects in a Chinese population to evaluate the association between a polymorphism in 3'-untranslated region of PTGS2, rs5275, and the risk of gastric cancer. Logistic regression analysis revealed that variant allele (C) of rs5275 was significantly associated with an increased risk of gastric cancer (per allele odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29, p = 0.030). This association was more prominent in females (per allele OR = 1.42, 95% CI = 1.11-1.81, p = 0.005) and nonsmokers (per allele OR = 1.35, 95% CI = 1.14-1.59, p = 0.001). Interestingly, we detected a negative interaction between rs5275 and smoking on the gastric cancer risk (p = 0.007). Our findings indicate that PTGS2 rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility.

A germline variant N375S in MET and gastric cancer susceptibility in a Chinese population.

MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF), play a pivotal role in the activties of tumor cells. A germline missense variant in exon 2 of the MET gene, N375S (rs33917957 A>G), may alter the binding affinity of MET for HGF and thus modify the risk of tumorigenesis. In this study, we performed a case-control study to assess the association between N375S and gastric cancer risk in 1,681 gastric cancer cases and 1,858 cancer-free controls. Logistic regression analysis was applied to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and gastric cancer risk. We found that MET N375S variant genotypes (NS/SS) were associated with a significantly decreased risk of gastric cancer (OR = 0.78, 95% CI = 0.63-0.96, P = 0.021) compared with the wildtype homozygote (NN). The finding indicates that this germline variant in MET may decrease gastric cancer susceptibility in Han Chinese.

Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population.

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.

Evaluation of the association between the AC3 genetic polymorphisms and obesity in a Chinese Han population.

BACKGROUND: AC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5-23.9), 677 overweight (BMI 24.0-27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623-0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P(80)) and 455 controls (BMI = P(20-50)) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses. CONCLUSIONS: The present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment.

A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population.

Interleukin-23 receptor (IL-23R) is a key element in T helper (Th)17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case-control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.68-0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR = 0.75, 95% CI = 0.65-0.87) other than in diffuse-type gastric cancer (adjusted allelic OR = 0.96, 95% CI = 0.76-1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population.

Genetic variation of PSCA gene is associated with the risk of both diffuse- and intestinal-type gastric cancer in a Chinese population.

Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study including 1,053 incident gastric cancer patients and 1,100 cancer-free controls in a high-risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR =1.37, 95% CI = 1.15-1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal-type gastric cancer (p = 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR = 1.14, 95% CI = 0.96-1.36). A small meta-analysis including 5 case-control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29-2.60 and OR = 1.84, 95% CI: 1.33-2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.

A 5'-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population.

OBJECTIVE: Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population. METHODS: Two variations in the 5'-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population. RESULTS: Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status (P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population. CONCLUSION: The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings.

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.

The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population.

Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factor-binding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulinlike growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio=1.84, 95% confidence interval=1.45-2.33 for 32Gly/Ala and odds ratio=2.39, 95% confidence interval=1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (Pint<0.001). These findings suggest that functional variants of insulin-like growth factor-binding protein-3 might be important markers for gastric cancer susceptibility and further studies are warranted to characterize the functional relevance of the locus-locus interaction of this gene.

TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case-control analysis in a Chinese population.

PURPOSE: 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). METHODS: Genotyping was performed using the primer-introduced restriction analysis-PCR assay in 255 ESCC cases and 704 cancer-free controls in a Chinese population. RESULTS: 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. CONCLUSIONS: 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.

Better understanding the influence of cigarette smoking and indoor air pollution on chronic obstructive pulmonary disease: a case-control study in Mainland China.

BACKGROUND AND OBJECTIVE: Although the association between COPD and smoking status (non-smoking, ex-smoking and current smoking) and indoor air pollution in Chinese populations is well established, the link between COPD and the number of cigarettes smoked has not been examined. This study investigated the relationship between the total amount of cigarettes smoked (TACS) and indoor air pollution, with the risk of COPD among urban and rural Chinese adults. METHODS: A nested case-control study was performed using data collected in a large community survey (N = 29 319) conducted between October 2000 and March 2001 in Nanjing, China. The exposure to indoor respiratory pollutants of cooking and heating materials and to passive cigarette smoke was compared in patients diagnosed with COPD (n = 1743) and controls matched for age, gender and residence (n = 1743). RESULTS: The smoking rate among COPD patients was significantly higher than that among the controls. After controlling for possible confounders, the adjusted odds ratios for COPD increased across TACS tertiles: from lower (OR = 1.40, 95% confidence interval (CI): 1.09-1.79), to middle (OR = 1.55, 95% CI: 1.21-1.99), and upper (OR = 1.77, 95% CI: 1.37-2.29). Among smokers, women were significantly more likely to develop COPD than men (OR = 1.20, 95% CI: 1.02-1.41). There were no significant associations between COPD and domestic fuels used, kitchen ventilation or passive smoking. Heating in winter with coal was weakly but positively linked with COPD among non-smokers overall, among women non-smokers, and specifically for women living in urban as well as rural areas. CONCLUSIONS: A clear dose-response relationship exists between cigarette smoking and COPD; compared with men, women smokers were more susceptible to COPD. Exposure to other respiratory pollutants in the home was not significantly associated with the diagnosis of COPD.

[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.

Association study between hypertension and A/G polymorphism at codon 637 of the transporter associated with antigen processing 1 gene.

To explore the effect of A/G polymorphisms at codon 637 of the transporter associated with antigen processing 1 (TAP1) gene on the risk of hypertension. A case-control study of epidemiology was conducted. The case group included 277 community-based patients (136 males and 141 females; mean age 58.7+/-12.1 years) diagnosed with hypertension, and the control group consisted of 227 healthy subjects (95 males and 132 females; mean age 51.29+/-12.16 years) from the same community. The A/G polymorphisms at codon 637 of the TAP1 gene was examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA. The effect of A/G polymorphisms at codon 637 of the TAP1 gene on hypertension was analyzed by using multivariate unconditional logistic regression models. The contribution of TAP1 637 A/G allele frequencies of the control group was consistent with that predicted by the Hardy-Weinberg equilibrium test (x2=230, p=0.632). There was a significant difference in the frequency of the A/G polymorphisms at codon 637 of the TAP1 gene between hypertensive patients (74.4/25.6%) and controls (82.4%/17.6%), x2=9.324, p=0.002. Genotype model (AA-AG-GG) analysis showed that there was a significant difference in the frequency of the recessive genotype between cases and controls (AA/AG vs. GG: odds ratio [OR]=3.046, 95% confidence interval [CI]=1.138-8.153) after adjustment for the covariates of age, serum total cholesterol, triglycerides, body mass index (BMI) and smoking. But there were no significant differences in the frequency of the genotype for the dominant model (AA vs. AG/GG: p=0.293) or additive model (AA vs. AG vs. GG: p=0.081) after adjustment. One-way ANOVA analysis showed that the systolic blood pressure, diastolic blood pressure, and BMI levels of the GG genotype were significantly higher than those of the AA or AG genotypes. In conclusion, our findings suggest that the A/G polymorphisms at codon 637 of the TAP1 gene contributes to the risk of hypertension, possibly via the increases in blood pressure and BMI.

[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.