Vitamin D and estrogen receptor gene polymorphisms and the risk of colorectal cancer in Bulgaria

Background and aims Different epidemiological studies report the protective effect on colorectal cancer (CRC) exerted by vitamin D₃ intake, estrogen replacement therapy, and increase of the risk of microsatellite instability (MSI) in CRC by withdrawal of estrogens. The aim of our study was to search for association between CRC and polymorphisms in estrogen receptor-α (ER-α) and Vitamin D receptor (VDR) genes. Materials and methods We analyzed the PvuII and XbaI polymorphisms from the ER-α gene and the BsmI polymorphism of the VDR gene in 140 patients with CRC (subsequently divided according to their MSI status) and 94 controls. Results We have demonstrated that the presence of the PvuII pp genotype increased the risk of developing MSI(+) tumors about three times compared to MSI(−) tumors [odds ratio (OR)=3.09, 95% confidence interval (CI) 0.88–10.91]. The effect of the XbaI xx genotype was similar (OR=2.08, 95% CI 0.49–8.81). Our results for the VDR BsmI polymorphism showed an increased risk for CRC in bb carriers (OR=1.8, 95% CI 0.81–4.05). Conclusion We conclude that PvuII and XbaI polymorphisms in the ER-α gene were associated with the risk of developing MSI in CRC patients. The BsmI polymorphism in the VDR gene was linked to the risk of developing CRC.     

Bisphosphonate use and gastrointestinal tract cancer risk: Meta-analysis of observational studies

AIM: To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS: Systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library to identify studies through January 2011. Search terms were “bisphosphonates” or trade names of the drugs, and “observational studies” or “cohort studies” or “case-control studies”. Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed: (1) observational studies (case-control or cohort studies) on bisphosphonate use; (2) with at least 2 years of follow-up; and (3) reported data on the incidence of cancer diagnosis. The DerSimonian and Laird random effects model were used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis. Subgroup meta-analyses were conducted for the type of cancer (esophageal, gastric and colorectal cancers). Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up (mean 5 years; subgroup 3 years) were included.RESULTS: Of 740 screened articles, 3 cohort studies and 3 case-control studies were included in the analyses. At first, 4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer. More than 124 686 subjects participated in the 3 cohort studies. The mean follow-up time in all of the cohort studies combined was approximately 3.88 years. The 3 case-control studies reported 3070 esophageal cancer cases and 15 417 controls, 2018 gastric cancer cases and 10 007 controls, and 11 574 colorectal cancer cases and 53 955 controls. The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls. The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer. Also no statistically significant association was found in a meta-analysis of long-term follow-up studies. There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis (RR 0.96, 95% CI: 0.65-1.42, I² = 52.8%, P = 0.076) and no statistically significant association with long-term follow-up (RR 1.74, 95% CI: 0.97-3.10, I² = 58.8%, P = 0.119). No negative association was found in the studies reporting the risk of gastric cancer (RR 0.89, 95% CI: 0.71-1.13, I² = 0.0%, P = 0.472). In case of colorectal cancer, there was no association between colorectal cancer and bisphosphonate use (RR 0.62, 95% CI: 0.30-1.29, I² = 88.0%, P = 0.004) and also in the analysis with long-term follow-up (RR 0.61, 95% CI: 0.28-1.35, I² = 84.6%, P = 0.011).CONCLUSION: Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk. However, this finding should be validated in randomized controlled trials with long-term follow-up.     

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

AimVitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients.MethodsA cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI).ResultsIn the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05–1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02–1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03–1.73; P = 0.03).ConclusionThe haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.     

Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes

Aim

The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D).

Methods

In this cross-sectional study of 277 patients, 25-hydroxyvitamin D was measured by radioimmunoassay. FokI, BsmI, ApaI and TaqI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. Analysis of covariance and logistic regression were performed.

Results

The study included 76 patients of Indian descent and 201 patients of African descent. The prevalence of vitamin D deficiency (< 20 ng/mL) was 42.6%. When patients were classified into groups with (G1) and without (G2) vitamin D deficiency, there were no significant differences in age, systolic blood pressure, low-density lipoprotein cholesterol and HbA_1c, although body mass index was significantly higher in G1. Vitamin D deficiency was significantly associated with increased diastolic blood pressure and triglyceride levels, and reduced high-density lipoprotein cholesterol (P < 0.05). Prevalence of vitamin D deficiency was decreased in patients carrying the f allele of FokI (OR: 0.52; P = 0.02) and the aa genotype of ApaI (OR: 0.46; P = 0.05). BsmI and TaqI SNPs were not associated with vitamin D deficiency.

Conclusion

The rate of vitamin D deficiency was high in our T2D patients, and was associated with the VDR gene FokI and ApaI polymorphisms and cardiovascular risk profile. Measurements of vitamin D may help to detect T2D patients with cardiovascular risk, and VDR polymorphisms might explain why vitamin D deficiency is so frequently seen in some T2D patients.     

Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies

AIM:To investigate the association between statin use and colorectal cancer risk,we conducted an updated meta-analysis of published studies.METHODS:We performed a comprehensive search for studies published up to July 2013.Eligible studies for this meta-analysis were either randomized controlled trials(RCTs)or observational studies(casecontrol or cohort)evaluating any exposure to statins and the risk of colorectal cancer.Two reviewers selected studies based on predefined inclusion criteria,and abstracted the data.Pooled relative risk(RR)estimates with their 95%CI were calculated using fixedand random-effects models.Then,we assessed the potential presence of publication bias and betweenstudies heterogeneity.To evaluate the results,we also performed a"leave-one-out"sensitivity analysis.RESULTS:A total of 40 studies,involving more than eight million subjects,contributed to the analysis.They were grouped on the basis of study design and,consequently,three separate meta-analyses were conducted.A similar modest reduction in the risk of colorectal cancer with statin use was observed,which was not statistically significant among RCTs(RR=0.89,95%CI:0.74-1.07;n=8),but reached statistical significance among cohort studies(RR=0.91,95%CI:0.83-1.00;n=13)and case-control studies(RR=0.92,95%CI:0.87-0.98;n=19).While we did not find significant evidence of selective outcome reporting or publication bias,substantial heterogeneity was detected,mainly among the observational studies.The sensitivity analysis confirmed the stability of our results.CONCLUSION:A modest reduction in risk of colorectal cancer among statin users cannot be disproved.Further targeted research is warranted.2014 Baishideng Publishing Group Co.,Limited.All rights     

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.     

Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population

AIM: To investigate prevalence and risk factors for colorectal neoplasms in adults aged 50 years, for whom screening is not recommended.METHODS: This cross-sectional study compared prevalence and characteristics of colorectal and advanced adenomas in patients aged 50 years who underwent colonoscopy screening with subjects aged ≥ 50 years. To evaluate risk factors for colorectal and advanced adenoma in young adults, we used multivariable logistic regression models. Colorectal neoplasm characteristics were evaluated and compared with those in older patients.RESULTS: Among 2819 patients included, prevalences of colorectal adenoma and advanced adenoma were 19.7% and 1.5%, respectively. As patient age increased, so did the prevalence of colorectal neoplasm. However, prevalence of advanced adenoma did not differ between age-groups 45-49 years and ≥ 50 years(OR = 0.43, 95%CI: 0.17-1.07, P = 0.070). In younger age-group( 50 years), colorectal adenoma was significantly associated with older age, waist circumference(OR = 1.72, 95%CI: 1.15-2.55, P = 0.008), and current smoking(OR = 1.60, 95%CI: 1.07-2.41, P = 0.023). Alcohol consumption was an independent risk factor for colorectal advanced adenoma(OR = 3.69, 95%CI: 1.08-12.54, P = 0.037). Multiple neoplasms and large neoplasms(≥ 1 cm) were more prevalent in subjects ≥ 50 years.CONCLUSION: Current screening strategies for colorectal cancer may need to be amended to account for patient age, especially in young subjects with abdominal obesity, current smoking and alcohol consumption.     

CYP2E1 PstI/RsaI polymorphism and colorectal cancer risk: A meta-analysis

AIM: To clarify the association between CYP2E1 PstI/RsaI polymorphism and susceptibility to colorectal cancer.METHODS: A meta-analysis based on 10 eligible case-control studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk.RESULTS: In comparison of the homozygote c2c2 and c2 carriers (c1c2 + c2c2) and the homozygous wild-type genotype (c1c1), no association was found between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk [odds ratio (OR) = 1.24 (95% CI: 0.93-1.66) for c2c2; OR = 1.02 (95% CI: 0.88-1.19) for c2 carriers]. In stratified analysis, Caucasians with c2c2 homozygote appeared to have an increased risk of colorectal cancer (OR = 2.67, 95% CI: 1.03-6.89, P = 0.043), no significant associations were found in other groups.CONCLUSION: c2c2 homozygote of CYP2E1 PstI/RsaI polymorphism may be associated with the increased risk of colorectal cancer in Caucasians, which needs further investigations.     

XbaI polymorphisms of apolipoprotein B gene: Another risk factor of gallstone formation after radical gastrectomy

AIM: To prospectively investigate the association between the XbaI polymorphisms of apolipoprotein B (APOB) gene and gallstone formation following gastrectomy.METHODS: The study was conducted between January 2005 and December 2006. A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaI polymorphisms of APOB gene (X⁺X^- group, n = 24 and X^-X^- group, n = 162) and compared. The XbaI polymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).RESULTS: The incidence of gallstone was significantly higher in the X⁺X^- group than in the X^-X^- group [54.2% vs 9.3%, RR = 5.85 (2.23-15.32), P < 0.001]. The serum levels of total cholesterol (TC) and low-density lipoprotein (LDL) were higher in the X⁺X^- than in the X^-X^- group (4.02 ± 1.12 vs 3.48 ± 0.88, P = 0.004 before surgery and 3.88 ± 1.09 vs 3.40 ± 0.86, P = 0.008 after surgery). LDL was 2.21 ± 0.96 vs 1.89 ± 0.84 (P = 0.042) before surgery and 2.09 ± 0.95 vs 1.72 ± 0.85 (P = 0.029) after surgery in the two groups. No relationship was found between XbaI polymorphisms and gallbladder motility.CONCLUSION: In Chinese patients after radical gastrectomy, X⁺ allele of APOB gene is another risk factor for the development of gallstone besides the gallbladder motility disorder after surgery.     

Amplifications of NCOA3 gene in colorectal cancers in a Chinese population

AIM: To investigate the copy number variation of NACO3 gene in colorectal cancer (CRC) and its correlation with tumor progression. METHODS: A total of 142 samples of case-matched CRC tissues and adjacent normal tissues were obtained from patients undergoing bowel resection. Quantitative real-time polymerase chain reaction method was used to investigate the copy number variations of NCOA3 as well as gene expression in the collected tissues. RESULTS: Copy number gains of NCOA3 were detected in 39 CRC samples (27.5%) and were correlatedwith tumor progression (χ2 = 6.42, P = 0.0112). Moreover, there was a positive correlation between copy number gain and mRNA over-expression of NCOA3 in CRCs (P = 0.0023). Expression level of NCOA3 mRNA was also enhanced in the CRC samples with unaltered copy numbers (3.85 ± 1.23 vs 2.71 ± 0.64, P 0.01). CONCLUSION: Sporadic colorectal cancers exhibit different mechanisms of NCOA3 regulation.     

Association between rs735482 polymorphism and risk of cancer: A meta-analysis of 10 case–control studies

Several studies have inspected the relationship between rs735482 polymorphism and the risk of some human cancers, but the findings remain controversial. We designed this meta-analysis to validate the association between rs735482 polymorphism and cancer risk. All articles were published before September 1, 2018 and searched in Pubmed, Embase, Web of Science, China National Knowledge Infrastructure, WangFang, and Chinese BioMedical databases, STATA 12.0 software was used for statistical analysis, which provides reasonable data and technical support for this article. A total of 10 studies were included in the meta-analysis, including 2652 cancer cases and 3536 rs735482 polymorphic controls. Data were directly extracted from these studies and odds ratios with 95% confidence intervals were computed to estimate the strength of the association. By pooling all eligible studies, the rs735482 polymorphism showed no significant association with susceptibility of several cancers in all the five genetic models (the allelic model: OR = 1.019, 95% CI: 0.916–1.134, P = .731). In addition, another adjusted OR data showed a significant increased risk between the rs735482 and susceptibility of several cancers (the codominant model BB vs AA: OR = 1.353, 95% CI: 1.033–1.774, P = .028) and the stratification analysis by ethnicity indicated the rs735482 is associated with an increased risk of cancer in Chinese group (BB vs AA, OR = 1.391, 95% CI = 1.054–1.837, P = .020; AB+BB vs AA OR = 1.253, 95% CI = 1.011–1.551, P = .039). However, the ERCC1 rs735482 is associated with a decreased risk of cancer in Italian group (AB vs AA, OR = 0.600, 95% CI = 0.402–0.859, P = .012; AB + BB vs AA, OR = 0.620, 95% CI = 0.424–0.908, P = .014). The results of this meta-analysis do not support the association between rs735482 polymorphism and cancer risk. But stratified analysis showed that rs735482 significantly increased the risk of cancer in Chinese while decreased the risk of cancer in Italian. Because of the limited number of samples, larger and well-designed researches are needed to estimate this association in detail.     

Association between oral contraceptive use and pancreatic cancer risk: A systematic review and meta-analysis

BACKGROUNDStudies on the association of oral contraceptive (OC) use and pancreatic cancer showed inconsistent findings. AIMTo evaluate the relationship between OC use and pancreatic cancer risk. METHODSA literature search for observational studies (case-control and cohort studies) was conducted up to December 2020. A meta-analysis was performed by calculating pooled relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s chi-square test and I² statistic. Subgroup analyses were performed by study design, source of controls in case-control studies, number of cases of pancreatic cancers, study quality according to Newcastle-Ottawa Scale score, geographical region and menopausal status. All analyses were performed using Review Manager 5.3 (RevMan 5.3).RESULTSA total of 21 studies (10 case-control studies and 11 cohort studies) were finally included in the present meta-analysis, comprising 7700 cases of pancreatic cancer in total. A significant association was observed between the ever use of OC and pancreatic cancer risk in the overall analysis (RR = 0.85; 95%CI = 0.73-0.98; P = 0.03). Duration of OC use (< 1 year, < 5 years, 5-10 years, > 10 years) was not significantly associated with the risk of pancreatic cancer. Subgroup analyses revealed a statistically significant subgroup difference for the geographic region in which the study was conducted (Europe vs Americas vs Asia; P = 0.07). Subgroup analyses showed a statistically significant decrease in pancreatic cancer risk and OC use in high-quality studies, studies conducted in Europe, and in postmenopausal women. CONCLUSIONDespite the suggested protective effects of OC use in this meta-analysis, further epidemiological studies are warranted to fully elucidate the association between the use of OC and pancreatic cancer risk.     

Vitamin D and polymorphisms of VDR gene in patients with systemic lupus erythematosus

The susceptibility for the development of systemic lupus erythematosus (SLE) is related to environmental, hormonal, genetic, and immunological factors. Numerous genes have been linked to the emergence of SLE, including vitamin D receptor (VDR) gene that synthesizes the receptor of vitamin D. Several polymorphisms have been described since the discovery of this gene, and their effects on VDR activity are still poorly understood. Vitamin D’s biological functions are mediated by VDR. Vitamin D exerts many actions on the immune system, and several studies have suggested its role in the pathogenesis of autoimmune diseases. SLE patients have low blood levels of vitamin D, which raises the possibility of association between the deficiency of this vitamin and the onset of the disease. BsmI and FokI polymorphic variants seem to be related to the onset of the disease in Asian patients. In this article, we review the aspects related to the metabolism and immunoregulatory effects of vitamin D, VDR, and main polymorphisms involving the VDR gene and the relationship between vitamin D levels and its receptor with SLE.     

Association of visceral obesity and early colorectal neoplasia

AIM:To examine whether visceral adipose tissue(VAT)serves as a risk factor for colorectal adenoma-early colorectal cancer(CRC)sequence.METHODS:A retrospective case-control study was conducted with 153 patients with stageⅠCRC,age/sex-matched 554 patients with colorectal adenoma and557 normal controls.All subjects underwent various laboratory tests,abdominal fat computed tomography(CT),and colonoscopy.VAT was defined as an intraabdominal adipose tissue area measured by CT scan.Adipose tissue area was measured at the level of the umbilicus from CT scan.We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.RESULTS:The body mass index(BMI),total cholesterol,fasting glucose and VAT areas were significantly different among normal,adenoma and CRC groups.The VAT area was 120.6±49.0 cm2in normal controls,130.6±58.4 cm2in adenoma group and 117.6±51.6cm2in CRC group(P=0.002).In univariate analysis,increased BMI was a risk factor for CRC compared to control(P=0.025).However,VAT area was not a risk factor for CRC compared to control.In multivariate analysis that adjusted for smoking,alcohol consumption and subcutaneous adipose tissue area,VAT area was inversely related to CRC,compared to the adenoma(OR=0.53,95%CI:0.31-0.92,highest quartile vs lowest quartile).CONCLUSION:Our study shows that visceral obesity is not a risk factor for early CRC.Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.     

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori -infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this metaanalysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

Value of bevacizumab in treatment of colorectal cancer: A meta-analysis

AIM:To assess the efficacy and safety of bevacizumab in the treatment of colorectal cancer.METHODS:All randomized controlled trials of bevacizumab for the treatment of colorectal cancer from January 2003 to June 2013 were collected by searching the Cochrane Library, Pub Med, Chinese National Knowledge Infrastructure and Wanfang databases.The primary endpoint was overall survival(OS), and the secondary endpoints were progression-free survival, overall response rate and adverse events.Two reviewers extracted data independently.Statistical analyses were performed with Stata 12.0.The degree of bias was assessed using funnel plots for the effect size of OS at the primary endpoint.RESULTS:Following the inclusion criteria and exclusion criteria, ten studies comprising 6977 cases were finally included, of which nine were considered to be of high quality(4-7 points) and one of low quality(1-3 points).Our meta-analysis revealed the efficacy of bevacizumab in patients with colorectal cancer in terms of OS(HR = 0.848, 95%CI:0.747-0.963), progressionfree survival(HR = 0.617, 95%CI:0.530-0.719), and overall response rate(OR = 1.627, 95%CI:1.199-2.207).Regarding safety, higher rates of grade ≥ 3 hypertension, proteinuria, bleeding, thrombosis, and gastrointestinal perforation were observed in the bevacizumab treatment group(P 0.05); however, the incidence of serious toxicity was very low.There was no publication bias in the 10 reports included in this meta-analysis.CONCLUSION:The clinical application of bevacizumab in colorectal cancer is effective with good safety.     

Clinical significance of CA19-9 in diagnosis of digestive tract tumors

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Systematic review of oncological outcomes following laparoscopic vs open total mesorectal excision

AIM: To systematically analyze the randomized trials comparing the oncological and clinical effectiveness of laparoscopic total mesorectal excision (LTME) vs open total mesorectal excision (OTME) in the management of rectal cancer.METHODS: Published randomized, controlled trials comparing the oncological and clinical effectiveness of LTME vs OTME in the management of rectal cancer were retrieved from the standard electronic medical databases. The data of included randomized, controlled trials was extracted and then analyzed according to the principles of meta-analysis using RevMan^® statistical software. The combined outcome of the binary variables was expressed as odds ratio (OR) and the combined outcome of the continuous variables was presented in the form of standardized mean difference (SMD).RESULTS: Data from eleven randomized, controlled trials on 2143 patients were retrieved from the electronic databases. There was a trend towards the higher risk of surgical site infection (OR = 0.66; 95%CI: 0.44-1.00; z = 1.94; P < 0.05), higher risk of incomplete total mesorectal resection (OR = 0.62; 95%CI: 0.43-0.91; z = 2.49; P < 0.01) and prolonged length of hospital stay (SMD, -1.59; 95%CI: -0.86--0.25; z = 4.22; P < 0.00001) following OTME. However, the oncological outcomes like number of harvested lymph nodes, tumour recurrence and risk of positive resection margins were statistically similar in both groups. In addition, the clinical outcomes such as operative complications, anastomotic leak and all-cause mortality were comparable between both approaches of mesorectal excision.CONCLUSION: LTME appears to have clinically and oncologically measurable advantages over OTME in patients with primary rectal cancer in both short term and long term follow ups.     

Diabetes mellitus carries a risk of gastric cancer:A metaanalysis

AIM:To investigate the association and quantify the relationship between diabetes mellitus(DM) and gastric cancer(GC) by an updated meta-analysis.METHODS:The initial PubMed search identified 1233publications. Studies not reporting GC or those not reporting actual number of GC were excluded. Twelve pertinent studies were retrieved from the PubMed database or from a manual search and considered for the meta-analysis. Pooled risk ratios and 95%CI were estimated by a random-effects model. Subgroup analysis was performed according to gender or geographical regions. Heterogeneity and publication bias were evaluated by I2and funnel plot analysis,respectively.RESULTS:DM was significantly associated with GC with a RR of 1.41(P = 0.006)(95%CI:1.10-1.81).Subgroup analyses revealed that both sexes showed a significant association with GC,with a greater magnitude of risk in females(RR = 1.90; 95%CI:1.27-2.85;P = 0.002) than in males(RR = 1.24; 95%CI:1.08-1.43;P = 0.002). In addition,the link between DM and GC was significant in East Asian DM patients(RR = 1.77;95%CI:1.38-2.26; P < 0.00001) but not in Western DM patients(RR = 1.23; 95%CI:0.90-1.68; P = 0.2).There was no evidence of publication bias,but the results indicated significant heterogeneity.CONCLUSION:This updated meta-analysis has provided evidence of positive DM-GC associations. The limited information on potentially important clinical confounding factors in each study deserves further investigation.