Hui Li

Publications (7)38.68 Total impact

• Article: The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.

  Ming Yang, Tong Sun, Yifeng Zhou, Li Wang, Li Liu, Xiaojiao Zhang, Xiaohu Tang, Mo Zhou, Pengqun Kuang, Wen Tan, Hui Li, Qipeng Yuan, Dianke Yu
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  ABSTRACT: Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk. Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 × 10(-5) ) or 2.54 (95% CI = 1.67-3.87, P = 1.36 × 10(-5) ), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged ≤60 years (OR = 3.10, 95% CI = 2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (P(interaction) = 5.64 × 10(-12) ). These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner. Cancer 2012. © 2012 American Cancer Society.
  Cancer 02/2012; 118(19):4681-6. · 4.77 Impact Factor
• Article: Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis.

  Jian Xu, Chen Wu, Xu Che, Li Wang, Dianke Yu, Tongwen Zhang, Liming Huang, Hui Li, Wen Tan, Chengfeng Wang, Dongxin Lin
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  ABSTRACT: Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the development and progression of various types of human cancer and serum miRNAs are potential biomarkers. This study examined whether some commonly deregulated miRNAs in hepatocellular carcinoma (HCC) are presented in serum of patients with HCC and can serve as diagnostic markers. Serum miRNAs (miR-21, miR-122, and miR-223) were quantified by real-time quantitative RT-PCR in 101 patients with HCC and 89 healthy controls. In addition, 48 patients with chronic type B hepatitis were also analyzed for comparison. We found that the median levels of miR-21, miR-122, and miR-223 were significantly higher in patients with HCC than those in healthy controls (P = 7.48 x 10⁻¹³, P = 6.93 x 10⁻⁹, and P = 3.90 x 10⁻¹², respectively). However, these elevated serum miRNAs were also detected in patients with chronic hepatitis (P = 2.05 x 10⁻¹², P = 4.52 x 10⁻¹⁶, and P = 1.65 x 10⁻¹¹, respectively). Moreover, serum miR-21 and miR-122 in patients with chronic hepatitis were higher than in patients with HCC (P = 3.99 x  10⁻⁴ and P = 4.97 x 10⁻⁸), although no such significant difference was found for miR-223. Receiver-operator characteristic (ROC) curve analyses suggest that these serum miRNAs may be useful markers for discriminating patients with HCC or chronic hepatitis from healthy controls, but not patients with HCC from patients with chronic hepatitis. Our results indicate that serum miR-21, miR-122 and miR-223 are elevated in patients with HCC or chronic hepatitis and these miRNAs have strong potential to serve as novel biomarkers for liver injury but not specifically for HCC.
  Molecular Carcinogenesis 02/2011; 50(2):136-42. · 3.16 Impact Factor
• Article: Interaction of cyclooxygenase-2 variants and smoking in pancreatic cancer: a possible role of nucleophosmin.

  Dan Zhao, Dongkui Xu, Xuemei Zhang, Li Wang, Wen Tan, Yongli Guo, Dianke Yu, Hui Li, Ping Zhao, Dongxin Lin
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  ABSTRACT: Overexpression of cyclooxygenase-2 (COX-2) is implicated in cancer development. This study examined the functional relevance of genetic polymorphisms in the COX-2 promoter and evaluated their associations with susceptibility to pancreatic cancer. Genotypes and haplotypes of COX-2 -765G/C, -1195G/A, and -1290A/G were analyzed in 393 pancreatic cancer patients and 786 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression.The function of the -765G-->C polymorphism was examined by a set of biochemical assays. The -1195AA or -765GC genotype carriers had a 1.34-fold (95% CI: 1.12-1.60) or 1.63-fold (95% CI: 1.25-2.10) excess risk for developing pancreatic cancer. These 2 variants showed a cooperative effect in context of haplotype, with the ORs for the A(-1195)-C(-765)- containing haplotypes being significantly greater than those for the G(-1195)-G(-765)-containing haplotypes. The -765C allele and smoking displayed a multiplicative joint effect, with an OR of 3.72 (95% CI: 1.70-8.14) for heavy smokers carrying the -765GC genotype. Biochemical assays suggest that the -765G-->C change creates a binding site for nucleophosmin (NPM) and phosphorylated NPM (p-NPM), which acts as a transcriptional inhibitor. Cigarette smoke remarkably increased COX-2 promoter activity, and this effect was more pronounced for the -765C allele compared with the -765G allele. Cigarette smoke reduced nuclear p-NPM levels, which was reversely associated with COX-2 expression. Functional COX-2 polymorphisms are associated with susceptibility to pancreatic cancer and tobacco smoke specifically increases -765C promoter activity, which might be mediated by p-NPM.
  Gastroenterology 05/2009; 136(5):1659-68. · 11.68 Impact Factor
• Article: Functional variants in cell death pathway genes and risk of pancreatic cancer.

  Ming Yang, Tong Sun, Li Wang, Dianke Yu, Xuemei Zhang, Xiaoping Miao, Junniao Liu, Dan Zhao, Hui Li, Wen Tan, Dongxin Lin
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  ABSTRACT: Fas-Fas ligand (FasL)-mediated death pathway is important in the life and death of immune cells and, therefore, influences immune surveillance of carcinogenesis. This study examined the association between functional variants of Fas (-1377G-->A and -670A-->G), FasL (-844T-->C), and caspase-8 (CASP8) six-nucleotide deletion polymorphism (-652 6N ins-->del) and risk of pancreatic cancer. Genotypes were determined in 397 cases with pancreatic cancer and 907 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression, and all statistical tests were two sided. We found a significant decrease in risk of pancreatic cancer associated with FasL and CASP8 but not Fas polymorphisms. Compared with noncarriers, the ORs of developing pancreatic cancer for FasL -844CT and TT carriers were 0.73 (95% CI, 0.57-0.94) and 0.35 (95% CI, 0.19-0.63), and for CASP8 -652 6N ins/del and del/del carriers were 0.65 (95% CI, 0.50-0.85) and 0.56 (95% CI, 0.33-0.98), respectively. Gene-gene interaction between the FasL and CASP8 variants further reduced the cancer risk in a multiplicative manner (OR for the presence of both FasL -844TT and CASP8 -652 6N del/del genotype, 0.10; 95% CI, 0.01-0.75). On the other hand, a multiplicative joint effect between the FasL -844CC or CASP8 -652 6N ins/ins genotype and smoking or diabetes mellitus in intensifying risk of pancreatic cancer was also evident. These results suggest that genetic variations in the death pathway genes FasL and CASP8 are involved in susceptibility to developing pancreatic cancer.
  Clinical Cancer Research 05/2008; 14(10):3230-6. · 7.74 Impact Factor
• Article: Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development.

  Dongxin Lin, Hui Li, Wen Tan, Xiaoping Miao, Li Wang
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  ABSTRACT: Folate deficiency has been associated with certain types of human cancer. We therefore investigated the effects of genetic polymorphisms in folate-metabolizing enzymes on the risk of developing gastroesophageal cancers in a Chinese population where folate deficiency is common. We found that functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS), two key enzymes involved in folate and methyl group metabolism, were significantly associated with increased risk of esophageal squamous cell carcinoma, gastric cardia carcinoma, and pancreatic carcinoma. The polymorphisms modulate risk of these cancers associated with low folate status. Our results suggest that MTHFR and TS genotypes may be determinant of gastroesophageal cancers in this at-risk Chinese population.
  Forum of nutrition 02/2007; 60:140-5.
• Article: Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer.

  Li Wang, Xiaoping Miao, Wen Tan, Xinghua Lu, Ping Zhao, Xiaohang Zhao, Yi Shan, Hui Li, Dongxin Lin
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  ABSTRACT: Human pancreatic cancer might be associated with folate deficiency and impaired metabolism. We tested this hypothesis by examining the contribution of functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) to risk of cancer. DNA from 163 pancreatic cancer patients and 337 control subjects was genotyped for MTHFR (677C > T and 1298A > C) and TS (5'-untranslated region tandem repeat and G/C). Association with risk of pancreatic cancer was estimated by logistic regression. All statistical tests were two-sided. We observed an increased risk of pancreatic cancer associated with the MTHFR 677CT (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.61-4.29; P = .0005) or 677TT (OR, 5.12; 95% CI, 2.94-9.10; P < .0001) genotype compared with the MTHFR CC genotype. An increased risk of pancreatic cancer was also associated with the TS 3Rc/3Rc genotype (OR, 2.19, 95% CI, 1.13-4.31; P = .022) compared with the TS 3Rg/3Rg genotype. Joint effect between MTHFR C677T polymorphism and smoking or drinking increased risk of pancreatic cancer in a super-multiplicative manner. The ORs for smoking, the polymorphism, and both factors combined were 0.70 (95% CI, 0.30-1.63), 2.17 (95% CI, 1.17-4.21), and 3.10 (95% CI, 1.54-6.51), respectively. This joint effect was much stronger in heavy smokers (OR, 6.69; 95% CI, 3.39-13.63; P < .0001). The ORs for drinking, the polymorphism, and both factors combined were 0.98 (95% CI, 0.40-2.30), 2.81 (95% CI, 1.65-4.98), and 4.39 (95% CI, 2.25-8.78), respectively. The MTHFR and TS polymorphisms are genetic determinants for developing pancreatic cancer.
  Clinical Gastroenterology and Hepatology 09/2005; 3(8):743-51. · 5.63 Impact Factor
• Article: Significant increase in risk of gastroesophageal cancer is associated with interaction between promoter polymorphisms in thymidylate synthase and serum folate status.

  Wen Tan, Xiaoping Miao, Li Wang, Chunyuan Yu, Ping Xiong, Gang Liang, Tong Sun, Yifeng Zhou, Xuemei Zhang, Hui Li, Dongxin Lin
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  ABSTRACT: Thymidylate synthase (TS) catalyzes the 5,10-methylene-tetrahydrofolate-mediated conversion of deoxyuridine monophosphate to deoxythymydine monophosphate, a nucleotide required for DNA synthesis and repair. The impaired TS expression has been shown to be related to 28 bp tandem repeats and a G-->C SNP in the 5'-UTR of TS. Folate deficiency has been demonstrated to play a role in gastroesophageal carcinogenesis. This case-control study was to examine the hypothesis that the TS polymorphisms, alone or in combination with serum folate status, may confer susceptibility of the hosts to gastroesophageal cancer. We analyzed TS genotype and serum folate concentration in 324 patients with esophageal squamous cell carcinoma (ESCC), 231 patients with gastric cardia adenocarcinoma (GCA) and 492 controls. It was found that compared with the normal expression TS genotype, the low expression TS genotype alone was significantly associated with increased risk of ESCC [adjusted odds ratio (OR) 1.47; 95% confidence interval (CI) 1.03-2.10] but not GCA (OR=0.98, 95% CI=0.68-1.40). More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Among subjects with low serum folate concentration (<3 ng/ml), the ORs of ESCC and GCA for the low expression genotype were 22.63 (95% CI=10.44-49.05) and 4.08 (95% CI=1.94-8.59), which were greater than respective 9.97 (95% CI=5.67-17.53) and 1.88 (95% CI=1.18-3.24) for the normal expression genotype (P=0.002 and 0.029). These results suggest an important role for folate deficiency and impaired TS activity in the etiology of ESCC and GCA.
  Carcinogenesis 08/2005; 26(8):1430-5. · 5.70 Impact Factor