Prevention of malignant digestive system tumors should focus on the control of chronic inflammation.

Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.

Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility.

Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5' and 3' untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.

Coffee consumption and risk of pancreatic cancer: a systematic review and dose-response meta-analysis.

The association between coffee consumption and pancreatic cancer risk has been extensively studied; however, there is no consistent conclusion. Therefore, this meta-analysis study sought to evaluate dose-response relationship between them. A search was conducted using the PubMed and Web of Science databases. Thirteen high-quality cohort studies were identified, involving in 959,992 study participants and 3831 pancreatic cancer cases. Comparing the highest with lowest categories of coffee intake, the pooled relative risk (RR) was 1.08 (95% CI 0.94-1.25). For dose-response analysis, no evidence of a nonlinear dose-response association between coffee consumption and pancreatic cancer (p for nonlinearity =0.171) was found. The risk of pancreatic cancer was increased by 5.87% (RR =1.06, 95% CI 1.05-1.07) with the increment of one cup/day. Coffee consumption was identified to be related with the increasing risk of pancreatic cancer in a dose-response manner. Nevertheless, further mechanistic studies are needed to clarify the concerned issues.

A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China with very low 5-year survival rate mostly due to the paucity of effective early diagnostic methods. Serum autoantibodies against 9 tumor-associated antigens (TAAs) from ESCC patients and healthy controls were detected by enzyme-linked immunosorbent assay to evaluate their performances in the immunodiagnosis of ESCC. Logistic regression models were generated to predict the probability of individuals being diagnosed with ESCC in training cohort (648 participants) and further validated in another independent cohort (372 participants). Finally, a panel of four TAAs showed high diagnostic accuracy with areas under the receiver operating characteristic curve of 0.838 in training cohort and 0.872 in validation cohort, respectively. The percentages of individuals correctly classified were 77.01 % in training cohort and 78.49 % in validation cohort, respectively. This model could discriminate early-stage (AJCC stage 0, I and II) ESCC patients from normal controls, with true-positive rate (TPR) of 67.57 % in training cohort and TPR of 63.33 % in validation cohort, and the overall TPR for early-stage ESCC was 66.85 % when the two cohorts were combined. The diagnostic performance of this model showed no significant difference between early-stage and late-stage (AJCC stage III and IV) ESCC patients. In summary, the optimized model with 4 TAAs has a high diagnostic performance for ESCC detection, especially for early-stage ESCC.

The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression.

Cervical cancer is a cause of cancer death, making it as the one of the most common cause for death among women globally. Though many studies before have explored a lot for cervical cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. We loaded gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles to cervical cancer cells due to the propertities of quercetin in ameliorating cellular processes and the easier absorbance of nanoparticles. Here, in our study, quercetin nanoparticles (NQ) were administrated to cells to investigate the underlying mechanism by which the cervical cancer was regulated. First, JAK2-inhibited carvical cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for cervical cancer progression. And the role of quercetin nanoparticles was determined during the process. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal cervical cells. And apoptosis and autophagy were found in JAK2-inhibited cancer cells through activating Caspase-3, and suppressing Cyclin-D1 and mTOR regulated by Signal Transducer and Activator of Transcription (STAT) 3/5 and phosphatidylinositide 3-kinase/protein kinases (PI3K/AKT) signaling pathway. The cervical cancer cells proliferation was inhibited. Further, tumor size and weight were reduced by inhibition of JAK2 in vivo experiments. Notably, administration with quercetin nanoparticles displayed similar role with JAK2 suppression, which could inhibit cervical cancer cells proliferation, invasion and migration. In addition, autophogy and apoptosis were induced, promoting cervical cancer cell death. To our knowledge, it was the first time to evaluate the role of quercetin nanoparticles in improving cervical cancer from apoptosis, autophagy and proliferation, which could be a potential target for future therapeutic approach clinically.

Distribution and clinical association of plasma soluble ST2 during the development of type 2 diabetes.

AIM: ST2 plays important roles in diabetes and cardiovascular diseases. However, the distribution and changes in plasma soluble ST2 during the development of type 2 diabetes remain unclear. METHODS: In the present study, 525 subjects were recruited and divided into three groups: normal, prediabetic and diabetic subjects. The sST2 levels of all subjects were measured using a high-sensitivity assay. RESULTS: sST2 levels were modestly but significantly elevated in patients with diabetes (26.1ng/ml) compared with normal subjects (19.3ng/ml, P<0.001) and persons with prediabetes (20.3ng/ml, P<0.001). The third and fourth quartiles (21.3 and 29.1ng/ml, respectively) of the sST2 levels were associated with a 2.31- and 4.00-fold increased risk of having diabetes. With the prediabetic group as a reference population, patients with sST2 levels in the fourth quartiles had a higher increased risk of having diabetes mellitus (odds ratios=2.19, P<0.05). Furthermore, each SD log sST2 was associated with a 1.57-fold increased risk of atherosclerosis when all relevant variables was added to the multivariable logistic regression models. After adjustment for age and sex, all markers of liver and renal function, HDL-cholesterol, total cholesterol and smoking status showed a significant association with sST2 levels. CONCLUSION: Elevated sST2 levels were not only associated with metabolic characteristics of diabetes but also with a significantly increased risk of having diabetes.

Competing endogenous RNA networks and gastric cancer.

Recent studies have showed that RNAs regulate each other with microRNA (miRNA) response elements (MREs) and this mechanism is known as "competing endogenous RNA (ceRNA)" hypothesis. Long non-coding RNAs (lncRNAs) are supposed to play important roles in cancer. Compelling evidence suggests that lncRNAs can interact with miRNAs and regulate the expression of miRNAs as ceRNAs. Several lncRNAs such as H19, HOTAIR and MEG3 have been found to be associated with miRNAs in gastric cancer (GC), generating regulatory crosstalk across the transcriptome. These MRE sharing elements implicated in the ceRNA networks (ceRNETs) are able to regulate mRNA expression. The ceRNA regulatory networks including mRNAs, miRNAs, lncRNAs and circular RNAs may play critical roles in tumorigenesis, and the perturbations of ceRNETs may contribute to the pathogenesis of GC.

Tumor associated antigens or anti-TAA autoantibodies as biomarkers in the diagnosis of ovarian cancer: a systematic review with meta-analysis.

OBJECTIVE: This systematic review aims to outline and summarize known tumor-associated antigens (TAAs) or anti-TAA autoantibodies and their diagnostic values in ovarian cancer (OC). METHODS: A systematic literature search was conducted in two databases. Data were independently extracted and reviewed by two junior investigators and the disagreement was further resolved by consulting one of the senior investigators. RESULTS: Sixty publications reporting 113 different TAAs or anti-TAA autoantibodies were included. The majority of the studies were conducted in western countries. CA125, p53 and HE4 were the most frequently tested TAAs in OC. Meta-analysis showed that there was a significant association between serum anti-p53 autoantibody and increased risk of OC. CONCLUSION: Serum TAAs or anti-TAA autoantibodies are promising diagnostic biomarkers in the detection of OC. A customized mini-array of multiple TAAs may enhance the detection of anti-TAA autoantibodies in OC. Additional studies with sufficient number of OC patients and carefully selected controls are needed to further verify the results.

Association of polymorphisms in X-ray repair cross complementing 1 gene and risk of esophageal squamous cell carcinoma in a Chinese population.

OBJECTIVES: To investigate the association between three single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing 1 gene (XRCC1) and the risk of esophageal squamous cell carcinoma (ESCC) in Chinese population. METHODS: A case-control study including 381 primary ESCC patients recruited from hospital and 432 normal controls matched with patients by age and gender from Chinese Han population was conducted. The genotypes of three XRCC1 polymorphisms at -77T>C (T-77C), codon 194 (Arg194Trp), and codon 399 (Arg399Gln) were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP). Unconditional logistic regression model and haplotype analysis were used to estimate associations of these three SNPs in XRCC1 gene with ESCC risk. RESULTS: Polymorphisms at these three sites in XRCC1 gene were not found to be associated with risk for developing ESCC; however the haplotype C(codon 194)G(codon 399)C(-77T>C) was significantly associated with reduced risk of ESCC (OR: 0.62, 95% CI: 0.40-0.96) upon haplotype analysis. CONCLUSION: These results suggested that the gene-gene interactions might play vital roles in the progression on esophageal cancer in Chinese Han population and it would be necessary to confirm these findings in a large and multiethnic population.

Genetic epidemiological analysis of esophageal cancer in high-incidence areas of China.

Genetic epidemiological studies have shown that genetic susceptibility to esophageal cancer (EC) is an important cause of its high incidence within families in some areas of China. The purpose of this study was to obtain evidence of a genetic basis of EC in Xin-an and Xin-xiang counties in China. Familial aggregation and complex segregation analyses were performed of 79 EC families in these counties. The heritability of EC was examined using Falconer's method and complex segregation analysis was conducted with the SEGREG program in Statistical Analysis for Genetic Epidemiology (SAGE version 5.3.1). The results showed that the distribution of EC in families did not fit well into a binomial distribution. The heritability of EC among first-degree and second- degree relatives was 67.0±7.31% and 43.1%±9.80%, respectively, and the summing up powered heritability was 53.2±6.74%. The segregation ratio was 0.045. Complex segregation analysis showed that the genetic model of EC was additive. The current results provide evidence for an inherited propensity to EC in certain high-risk groups in China, and support efforts to identify the genes that confer susceptibility to this disease.

Mini-array of multiple tumor-associated antigens (TAAs) in the immunodiagnosis of esophageal cancer.

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

Bioinformatic prediction of SNPs within miRNA binding sites of inflammatory genes associated with gastric cancer.

Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-κB and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

CYP1A1 genetic polymorphisms and risk for esophageal cancer: a case-control study in central China.

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.

The methylenetetrahydrofolate reductase C677T polymorphism influences risk of esophageal cancer in Chinese.

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese.

[Correlation between tag single nucleotide polymorphisms of microRNA regulatory genes and the genetic susceptibility of primary liver cancer].

OBJECTIVE: This study aimed to understand the correlation between tag single nucleotide polymorphisms (tSNP) of microRNA regulatory genes and the gentic susceptibility of primary liver cancer. METHODS: 1:1 case-control study was applied in this research. A total of 532 primary liver cancer patients in 2 teaching hospitals in Zhengzhou city were enrolled as case group.532 healthy individuals were enrolled as control group. The subjects were surveyed by a face-to-face interview and 5 ml of peripheral venous blood were collected. Candidate tSNP were screened from DICER1, RAN and GEMIN4 gene, respectively. PCR-RFLP or Allele specific PCR was applied for genotyping of the subjects. Conditional logistic regression model and Multifactor-Dimensionality Reduction method were applied for analyzing the correlation between tSNP of above genes and gentic susceptibility of primary liver cancer. The gene-environment interaction was also analyzed. RESULTS: The frequencies of genotype CC, CT, TT in rs14035 locus were 67.29% (358/532), 28.20% (150/532), 4.51% (24/532) in case group, and 70.30% (374/532), 28.20% (150/532), 1.50% (8/532) in control group, respectively (χ2=8.35, P<0.05). The frequencies of genotype GG, GA, AA in rs1045491 locus were 71.05% (378/532), 26.69% (142/532), 2.26% (12/532) in case group, and 80.45% (428/532), 18.42% (98/532), 1.13% (6/532) in control group, respectively (χ2=13.17, P<0.01); the frequencies of genetype GG, GT, TT in rs2291778 locus were 53.38% (284/532), 40.23% (214/532), 6.39% (34/532) in case group, and were 25.94% (138/532), 63.91% (340/532), 10.15% (54/532) in control group (χ2=83.71, P<0.01). TT genotype in rs14035 locus (OR=2.54, 95%CI: 1.19-6.32) and GA genetype in rs1045491 locus (OR=1.74, 95%CI: 1.08-2.66) were susceptible genotype of primary liver cancer, whereas GT (OR=0.52, 95%CI: 0.43-0.75) and TT genotype (OR=0.62, 95%CI: 0.46-0.86) in rs2291778 locus were protective genotype. Haplotype analysis showed that haplotype 3 (AACTGGGT) (OR=1.42, 95%CI: 1.10-1.82) and haplotype 5 (AGCCAGCC) increased the risk of occurrence of primary liver cancer (OR=1.36, 95%CI: 1.02-1.80), whereas haplotype 2 (AACTATCC) (OR=0.69, 95%CI: 0.52-0.91) and haplotype 6 (AACTGTGT)(OR=0.61, 95%CI: 0.45-0.81) decreased the risk. Subjects exposed to allele A of rs1045491, allele T of rs14035 and HBV infection intend to be the high risk population of primary liver cancer (OR = 3.72, 95%CI: 2.38 - 5.56). CONCLUSION: Genotypes of TT in rs14035 locus, and GA in rs1045491 locus may be susceptible genotypes of liver cancer carcinogenesis. T allele in rs2291778 locus is a non-susceptible allele of primary liver cancer. Combined effects of multigene alleles and multi-locus genotype may have a synergistic role in the carcinogenesis of liver cancer.

[Improvement on PCR-CTPP: a SNP genotyping approach based on mismatch technique].

To explore the technique principle of PCR with confronting two-pair primers (PCR-CTPP) and improve the accuracy of SNP genotyping by taking the 1298 locus of human gene MTHFR as an example, the reliability between conventional PCR-CTPP and improved PCR-CTPP was compared using reconstructed PCR-CTPP detecting system in terms of designing appropriate primers and optimizing annealing temperature and the final concentration of primers. The improved PCR-CTPP detection system proved to be more accurate, which supported the viewpoint on the theoretical defects of conventional PCR-CTPP. The large-scale study verified the reliability of the improved method. It is expected that this improved technique would be widely used in the field of medicine and molecular biology.

[Population-based case-control family study on risk factors of esophageal cancer in high incidence area].

OBJECTIVE: To explore the risk factors of esophageal cancer (EC) in the high-incidence regions, so as to provide scientific evidence for taking effective prevention measures. METHODS: A population based case-control family study was carried out. 1711 case family members in 505 families in which one of the couple or their first degree relatives suffered from EC were selected from high incidence in Henan province. Control families without neoplasm were selected from the same villages in matching conditions of age, sex, and family members. All information of case and control families was collected by Questionnaire of Life and Health of Inhabitant. The data were analyzed with logistic regression model. RESULTS: Compared with the control families,it was shown that hobby for smoked food [2.10% (36/1711), 0.82% (14/1711); chi2 = 9.82, P = 0.00; OR = 2.61, 95% CI: 1.40 - 4.85], hobby for fried food [7.17% (66/921), 3.91% (35/894) ; chi2 = 9.13, P = 0.00; OR = 1.90, 95% CI: 1.24 -2.89], hobby for raw and hard food [13.36% (123/921), 8.95% (80/894); chi2 = 8.87, P =0.03; OR =1.57, 95% CI: 1.16 - 2.11], and hobby for hot food [20.05% (343/1711), 15.20% (260/1711); chi2 = 13.87, P= 0.00; OR= 1.40, 95% CI: 1.17 - 1.67], the history with mental stimulated [6.72% (115/1711), 3.10% (53/1711); chi2 = 24.06, P = 0.00; OR = 2.25, 95% CI: 1.62 -3.14], upper digestive symptom history [19.40% (332/1711), 12.74% (218/ 1711); chi2 = 28.15, P = 0.00; OR= 1.65, 95% CI: 1.37 - 1.99] entered the last model, and were responsible for the higher risk of EC. Eating fast was shown to be a protective factor [20.85% (192/921), 25.14% (225/895); chi2 = 4.73, P =0.03; OR = 0.78, 95% CI: 0.63 - 0.98]. CONCLUSION: EC is a kind of malignant tumor caused by multiple factors. Prevention and control of EC should be initiated from environmental factors, life style, genetic factors and social-psychological factors comprehensively.

[DNA repair gene xeroderma pigmentosum group D 751 polymorphism and the risk on esophageal cancer: a meta-analysis].

OBJECTIVE: To explore the association between XPD codon 751 polymorphism and esophageal cancer (EC) by systematically reviewing the risk of the original studies. METHODS: A comprehensive search was conducted to identify all case-control studies of XPD codon 751 polymorphism and EC risk. Meta-analysis was applied with Rev Man 4.2 software for calculation of pooled OR value (with 95% CI) of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). RESULTS: Of the 12 case-control studies selected for this Meta-analysis, a total of 2558 EC cases and 5122 controls were included. Compared with the wild-type homozygote Lys/Lys, the pooled Odds Ratios (with 95% CI) of Lys/Gln, Gln/Gln, (Lys/Gln + Gln/Gln) genotypes of XPD codon 751 polymorphism for EC risk were 1.19 (1.05, 1.34), 1.22 (0.86, 1.74), 1.20 (1.01, 1.42), respectively. In a stratified analysis, a total of 1417 ESCC cases and 2312 controls were included, and individuals carrying Lys/Gln genotype or (Lys/Gln + Gln/Gln) had 1.22-fold or 1.24-fold excess risks for ESCC compared with those carrying Lys/Lys genotype. A total of 935 EAC cases and 2604 controls were included, and none of the genotype of XPD codon 751 genetic polymorphism was found to be related to EAC. CONCLUSION: Both heterozygote Lys/Gln and (Lys/Gln + Gln/Gln) for XPD codon 751 genetic polymorphism were associated with an increased risk of developing esophageal cancer. Furthermore, heterozygote Lys/Gln and (Lys/Gln + Gln/Gln) for XPD codon 751 genetic polymorphism might have increased the risk of ESCC, but have no association with EAC.

[Study on the association of cytochrome P450 polymorphisms and the risk of esophageal cancer: a meta-analysis].

OBJECTIVE: To examine the association between CYP1A1 polymorphisms (MspI and Ile/Val) and esophageal cancer (EC) by systematically reviewing the risk of the original studies. METHODS: Data from 16 papers (8 for MspI, 14 for Ile/Val) regarding case-control studies on the association of cytochrome P450 polymorphisms and risk of esophageal cancer was analyzed by dominant model (variant genotype vs. wild-type genotype) through meta-analysis. Stratified analysis was carried out according to the pathological types. RESULTS: In systematical analysis, CYP1A1 MspI variant genotype (TC + CC) had no association with EC risk (OR = 1.17, 95%CI: 0.82 - 1.66). Similar results were observed in esophageal squamous-cell carcinoma (ESCC) (OR = 1.17, 95%CI: 0.82 - 1.69) and esophageal adenocarcinoma (EAC) (OR = 1.39, 95%CI: 0.67 - 2.09). Individuals with the CYP1A1 Ile/Val variant genotype (Ile/Val + Val/Val) had an increased risk for EC, when comparing with wild type (Ile/Ile), with an OR of 1.39 (95%CI: 1.07 - 1.80). CYP1A1 Ile/Val variant genotype could increase the risk of ESCC (OR = 1.43, 95%CI: 1.07 - 1.91) but no significant association was found with EAC (OR = 1.20, 95%CI: 0.62 - 2.30). CONCLUSION: CYP1A1 gene polymorphism Ile/Val might have played a role in the development of ESCC but CYP1A1 MspI polymorphism might not be associated with the susceptibility of EC.

[Influential factors of Hardy-Weinberg equilibrium on the study of association between gene polymorphism and disease].

OBJECTIVE: According to the data collected from gastric cancer families comparative study, the influence factors of Hardy-Weinberg (H-W) equilibrium in the association studies of gene polymorphism and disease were analyzed to reveal the reasons that affecting the equilibrium deviation in the group. METHODS: Varieties of risk genotype for gastric cancer were analyzed and detected with H-W equilibrium, genetic linkage disequilibrium analysis and Cochran-Armitage trend test. RESULTS: (1) Significant deviations from H-W equilibrium were observed in IL-1B-31, IL-1B-511, IL-1RN and TNF-A-308 of the cases and controls (P < 0.01). MIF-173 tended to be equilibrium in the population. (2) Deviations from expectations of phenotypes combination probability were observed in two-site H-W chi(2) tests (P < 0.01). (3) The Cochran-Armitage trend test showed that distribution of IL-1B-511 and IL-1RN were significantly different (P < 0.05), suggesting that population stratification might have existed in the group. CONCLUSIONS: (1) Affected by frequency-dependent selection, under the combination of linkage disequilibrium, mutations and interaction, genotype frequency of IL-1B-31, IL-1B-511, IL-1RN and TNF-A-308 showed deviation from H-W equilibrium in population. (2) Two-site genetic equilibrium test model seemed better to reflect the differences of phenotypic combination fitness. (3) Population stratification was another factor to express the deviation from H-W equilibrium.