Weifeng Tang

Vascular endothelial growth factor A polymorphisms are associated with increased risk of coronary heart disease: a meta-analysis

Coronary heart disease (CHD) is a common complex disease resulting from the interaction of multiple environmental and genetic factors. To assess the potential relationship of vascular endothelial growth factor (VEGFA) rs699947 C>A, rs3025039 C>T and rs2010963 G>C polymorphisms with CHD risk, a comprehensive meta-analysis was conducted. A systematic search of EMBASE and PubMed online database for publications on VEGFA polymorphisms and risk of CHD was carried out. Crude Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated to determine the association. A total of ten publications including 22 trails involving 2097 cases and 2867 controls were included in our pooled analysis. Overall, results of the present meta-analysis demonstrated a significant association between VEGFA rs699947 C>A polymorphism and an increased risk of CHD. After stratifying by ethnicity and CHD type, the association was also obtained. A significant association between VEGFA rs3025039 C>T polymorphism and risk of CHD was also found. For VEGFA rs2010963 G>C polymorphism, the polymorphism was associated with MI risk. In conclusion, our findings suggest that VEGFA rs699947 C>A, rs3025039 C>T and rs2010963 G>C polymorphisms are risk factors for CHD. In the future, large sample size and well-designed epidemiologic studies are needed to confirm these conclusions.

Investigation of cyclin D1 rs9344 G>A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects

The relationship between cyclin D1 (CCND1) rs9344 G>A polymorphism and colorectal cancer (CRC) risk is still ambiguous. To obtain a precise estimation of the relationship, we performed an extensive meta-analysis based on the eligible studies. Crude odds ratios with their 95% confidence intervals were harnessed to determine the strength of correlation between CCND1 rs9344 G>A polymorphism and CRC risk under the allele, the homozygote, the dominant, and the recessive genetic models, respectively (28 studies with 5,784 CRC cases and 7,858 controls). Our results indicated evidence of the association between CCND1 rs9344 G>A polymorphism and the increased risk of CRC in four genetic models: A vs G, AA vs GG, AA+GA vs GG, and AA vs GA+GG. In a stratified analysis by cancer type of CRC, there was an increased risk of sporadic CRC found in three genetic models: A vs G, AA vs GG, and AA+GA vs GG. In a stratified analysis by ethnicity, there was an increased CRC risk found among Asians in allele comparison genetic models, as well as Caucasians in two genetic models: AA+GA vs GG and A vs T. In summary, this meta-analysis demonstrates that CCND1 rs9344 G>A polymorphism may be a risk factor for CRC.

Relationship of PPARG , PPARGC1A , and PPARGC1B polymorphisms with susceptibility to hepatocellular carcinoma in an eastern Chinese Han population

Background PPARG, PPARGC1A, and PPARGC1B polymorphisms may be implicated in the development of cancer. Participants and methods In this study, we selected PPARG rs1801282 C>G and rs3856806 C>T, PPARGC1A rs2970847 C>T, and PPARGC1B rs7732671 G>C and rs17572019 G>A single-nucleotide polymorphisms to explore the relationship between these polymorphisms and hepatocellular carcinoma (HCC) risk. A total of 584 HCC patients and 923 controls were enrolled. Results We found that PPARG rs1801282 C>G polymorphism was correlated with a decreased susceptibility of HCC (CG vs CC, adjusted OR 0.47, 95% CI 0.27–0.82, P=0.007; CG/GG vs CC, adjusted OR 0.52, 95% CI 0.31–0.88, P=0.015). However, PPARG rs3856806 C>T polymorphism was a risk factor for HCC (TT vs CC, adjusted OR 2.33, 95% CI 1.25–4.36, P=0.008; TT vs CT/CC, adjusted OR 2.26, 95% CI 1.22–4.17, P=0.010). In a subgroup analysis by chronic hepatitis B virus (HBV)-infection status, age, sex, alcohol use, and smoking status, a significant association between PPARG rs1801282 C>G polymorphism and a decreased risk of HCC in male, ≥53 years, never-smoking, never-drinking, and nonchronic HBV-infection-status subgroups was found. However, we found PPARG rs3856806 C>T polymorphism increased the risk of HCC in never-smoking, never-drinking, and nonchronic HBV-infection-status subgroups. Haplotype-comparison analysis indicated that Crs1801282Trs3856806Crs2970847Grs7732671Grs17572019, Crs1801282Trs3856806Trs2970847Grs7732671Grs17572019, and Crs1801282Crs3856806Crs2970847Crs7732671Ars17572019 haplotypes increased the risk of HCC. PPARG Crs1801282Trs3856806 and Grs1801282Crs3856806 haplotypes also influenced the risk of HCC. Conclusion In conclusion, our findings suggest PPARG polymorphisms may influence the susceptibility of HCC. The PPARG, PPARGC1A, and PPARGC1B haplotypes might be associated with HCC risk.

Investigation of LEP and LEPR polymorphisms with the risk of hepatocellular carcinoma: a case–control study in Eastern Chinese Han population

Background Leptin (LEP) and LEP receptor (LEPR) polymorphisms may be associated with the development of cancer. Methods In this study, we selected five functional LEP and LEPR single-nucleotide polymorphisms (SNPs) and conducted a case–control study to determine the relationship of LEP and LEPR polymorphisms with hepatocellular carcinoma (HCC) risk in Eastern Chinese Han population. There were 584 HCC cases and 923 cancer-free controls included in our study. HCC patients and controls were fully matched by age and sex. SNPscan™ genotyping method was used to analyze the genotyping of LEP rs2167270 G>A, rs7799039 A>G, LEPR rs6588147 G>A, rs1137100 G>A, and rs1137101 G>A SNPs. Results We found that LEP rs7799039 A>G and rs2167270 G>A polymorphisms were associated with the susceptibility of HCC in this population (LEP rs7799039 A>G: GG vs AA: adjusted odds ratio [OR]=2.03, 95% CI, 1.22–3.38, P=0.006 and GG vs AA/AG: adjusted OR=1.97, 95% CI, 1.20–3.22, P=0.007; rs2167270 G>A: AA vs GG: adjusted OR=2.03, 95% CI, 1.10–3.75, P=0.024 and AA vs GG/GA: adjusted OR=2.01, 95% CI, 1.10–3.68, P=0.023). However, LEPR rs6588147 G>A polymorphism decreased the risk of HCC (GA vs GG: adjusted OR=0.62, 95% CI, 0.45–0.86, P=0.005 and AA/GA vs GG: adjusted OR=0.64, 95% CI, 0.47–0.88, P=0.007). Conclusion This case–control study highlights that LEP rs7799039 A>G and rs2167270 G>A polymorphisms increase the susceptibility to HCC; however, LEPR rs6588147 G>A polymorphism may be a protective factor for HCC in Eastern Chinese Han population.

CTLA4 tagging polymorphisms and risk of colorectal cancer: a case–control study involving 2,306 subjects

Background CTLA4 is a candidate gene which has been implicated in the development of colorectal cancer (CRC). Patients and Methods To determine the important role of CTLA-4 polymorphisms on risk of CRC, we genotyped four CTLA-4 tagging polymorphisms and calculated crude/adjusted ORs with their 95% CIs. We recruited 1,003 sporadic CRC cases and 1,303 controls. Results The findings suggested that CTLA-4 rs231775 G>A polymorphism increased the risk of CRC (homozygote model: adjusted OR=1.40, 95% CI=1.05–1.87, P=0.022; dominant model: adjusted OR=1.19, 95% CI=1.00–1.41, P=0.047; and recessive model: adjusted OR=1.38, 95% CI=1.05–1.82, P=0.021). In a stratified analysis by site of tumor, this association was also found in colon cancer. We also found that CTLA-4 rs231775 GA/AA genotypes might be associated with an increased risk of CRC in Zhenjiang cohort. In addition, we found the CTLA-4 rs16840252 C>T polymorphism was associated with the risk of colon cancer. Haplotype comparison analysis showed that CTLA-4 Grs3087243Crs16840252Crs733618 Ars231775, Grs3087243Crs16840252Trs733618Ars231775, and other haplotypes increased the risk of CRC (P<0.001, <0.001, and 0.002, respectively). Conclusion This study evidences an association of CTLA-4 tagging polymorphisms and haplotypes with CRC risk. Additional well-designed studies with large sample sizes are required to confirm our findings.

PPARG c.1347C>T polymorphism is associated with cancer susceptibility: from a case-control study to a meta-analysis

Recently, several studies suggested that PPARG c.1347C>T polymorphism was correlated with cancer risk. However, past results remained controversial. In this study, we performed a case-control study on the relationship of PPARG c.1347C>T polymorphism with risk of non-small cell lung cancer (NSCLC) and subsequently carried out a meta-analysis to further assess the association between PPARG c.1347C>T and overall cancer. In our case-control study, after adjusting by age, sex, body mass index (BMI), smoking and drinking, a tendency to increased NSCLC risk was noted (CT/TT vs. CC: adjusted OR, 1.21; 95% CI, 0.97–1.51; P = 0.097). In the meta-analysis, we found a significant association between PPARG c.1347C>T polymorphism and overall cancer risk (T vs. C: OR, 1.13; 95% CI, 1.03–1.23; P = 0.006; TT vs. CC: OR, 1.29; 95% CI, 1.07–1.56; P = 0.008, CT/TT vs. CC: OR, 1.11; 95% CI, 1.02–1.21; P = 0.014 and TT vs. CT/CC: OR, 1.26; 95% CI, 1.04–1.52; P = 0.016). In a subgroup analysis by ethnicity, evidence of significant association between PPARG c.1347C>T polymorphism and cancer risk was found among Asians and mixed populations. In a subgroup analysis by cancer type, PPARG c.1347C>T polymorphism was associated with risk of esophageal cancer and glioblastoma. In addition, in a subgroup analysis by origin of cancer cell, evidence of significant association between PPARG c.1347C>T polymorphism and cancer risk was also found among epithelial tumor. In conclusion, the findings indicate PPARG c.1347C>T polymorphism may increase the susceptibility of cancer.

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 Chinese Han subjects

In this study, we aimed to determine the potential association of MTHFR tagging single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric junction adenocarcinoma (EGJA). MTHFR rs1801133 G>A, rs3753584 T>C, rs4845882 G>A, rs4846048 A>G and rs9651118 T>C polymorphisms were genotyped in 1,677 healthy individuals and 1,063 patients with EGJA. We found that MTHFR rs1801133 G>A polymorphism was significantly associated with the risk of developing EGJA (AA vs. GG: adjusted P = 0.001; GA/AA vs. GG: adjusted P = 0.007 and AA vs. GA/GG: adjusted P = 0.001). However, for MTHFR rs4845882 G>A polymorphism, the decreased risk of EGJA was found in two genetic models (AA vs. GG: adjusted P = 0.002 and AA vs. GA/GG: adjusted P = 0.005). In addition, for MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms, a tendency to decreased risk of EGJA was noted. In a subgroup analysis, a significantly decreased risk of EGJA in <64 years subgroup was identified. We found that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Crs9651118, Grs1801133Crs3753584Ars4845882Ars4846048Trs9651118 and Grs1801133Trs3753584Ars4845882Grs4846048Trs9651118 haplotypes significantly decreased the risk of EGJA (P = 0.002, P < 0.001 and P = 0.038, respectively). In conclusion, our study demonstrates that MTHFR rs1801133 G>A may be associated with the increased risk of EGJA. Meanwhile, MTHFR rs3753584 T>C, rs4845882 G>A and rs9651118 T>C polymorphisms and haplotypes may decrease the risk of EGJA in Eastern Chinese Han population. Further studies with large sample size and detailed gene-environmental data are needed to validate our conclusion.

The relationship between IGF2BP2 and PPARG polymorphisms and susceptibility to esophageal squamous-cell carcinomas in the eastern Chinese Han population

The aim of this case–control study was to assess whether PPARG and IGF2BP2 polymorphisms confer susceptibility to esophageal squamous-cell carcinoma (ESCC). A total of 507 patients pathologically confirmed for ESCC and 1,496 age-, sex-, and residence-matched healthy individuals were enrolled. The PPARG rs1801282 C>G and rs3856806 C>T and IGF2BP2 rs1470579 A>C and rs4402960 G>T polymorphisms were selected and genotyped by SNPscan genotyping assays. Multivariable logistic analysis suggested that the PPARG rs3856806 C>T polymorphism might increase the risk of ESCC. In different stratified analyses, there were significant associations between PPARG rs3856806 C>T and risk of ESCC in female, never-smoking, drinking, and never-drinking subgroups. In addition, we also found that PPARG rs1801282 C>G increased ESCC risk in the never-smoking subgroup. There was significant difference in Crs1470579Grs4402960Crs1801282Crs3856806-haplotype distribution among ESCC cases and control subjects. In conclusion, our findings highlight that PPARG rs1801282 C>G and rs3856806 C>T polymorphisms are candidates for susceptibility to ESCC in the eastern Chinese Han population. The Crs1470579Grs4402960Crs1801282Crs3856806 haplotype is associated with susceptibility to ESCC.