Sulphonylureas and cancer: a case–control study

This study was aimed at the assessment of incidence of malignancies in type 2 diabetic patients treated with different sulphonylureas. A matched case–control study was performed. Cases were 195 diabetic patients aged 69.0 ± 9.2 years who had an incident malignancy. Controls were 195 diabetic patients, unaffected by cancer, who were matched with the corresponding case for age, sex, duration of diabetes, BMI, HbA1_c, comorbidity, smoking and alcohol abuse. Exposure to hypoglycaemic drugs during the 10 years preceding the event (or matching index date) was assessed. After adjusting for concomitant therapies, exposure to metformin and gliclazide for more than 36 months was associated with a significant reduction in the risk of cancer (adj. ORs with 95% CI: 0.28 (0.13–0.57), p < 0.001, and 0.40 (0.21–0.57), p = 0.004, respectively). Conversely, use of glibenclamide for at least 36 months was associated with increased incidence of malignancies (adj. OR 2.62 (1.26–5.42); p = 0.009). Treatment with insulin, thiazolidinediones, or acarbose, was not associated with significant differences in the incidence of cancer. Long-term treatments with individual sulphonylureas could have differential effects on the risk of cancer. In particular, the possible protective effect of gliclazide, as well as the risk associated with glibenclamide, deserves further investigation.     

Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case–control study

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene–environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95 % CI 1.04–3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95 % CI 1.06–6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95 % CI 1.54–8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.     

COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

Meta-analysis of the association between VEGF-634 G>C and risk of malignancy based on 23 case–control studies

Purpose  

The association between polymorphism of vascular endothelial growth factor (VEGF)-634 G>C and malignancy risk has been widely studied, and no conclusive result was available up to now.     

The prevalence of colorectal neoplasia in patients with end-stage renal disease: a case–control study

BACKGROUND AND PURPOSE: The scarcity of organs for transplantation has led to aggressive pretransplant evaluations. Many younger kidney transplant patients with end-stage renal disease, who would be ordinarily at average risk for colorectal cancer, undergo screening colonoscopy as part of this evaluation. The purpose of this study was to determine the prevalence of colorectal neoplasia in patients with end-stage renal disease who are potential transplant candidates. MATERIALS AND METHODS: We performed a retrospective chart review analysis on 57 kidney transplant candidates who underwent pretransplant screening colonoscopy between August 1999 and December 2004. The control group was comprised of 60 age- and gender-matched subjects without end-stage renal disease who underwent routine screening colonoscopy. RESULTS: The prevalence of polyps in end-stage renal disease patients was 37 vs 22% in the control group (p = 0.07, not significant). None of the risk factors studied were found to predict the presence of polyps in the study group. CONCLUSION: These results suggest that screening guidelines for colorectal cancer for the general population should be adequate for potential kidney transplant recipients.     

Association between NOD2 single nucleotide polymorphisms and Grade III–IV acute graft-versus-host disease: A meta-analysis

Abstract

Objectives

The effects of NOD2 single nucleotide polymorphisms (SNPs) on Grade III–IV acute graft-versus-host disease (aGVHD) risk are somewhat contradictory in different studies. The aim of the meta-analysis was to clarify the effects of NOD2 SNPs on the incidence of Grade III–IV aGVHD.

Methods

We searched PubMed, EMBASE, Web of SCIENCE, WanFang and Chinese National Knowledge Infrastructure (CNKI) databases to collect eligible publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between NOD2 polymorphisms and Grade III–IV aGVHD risk.

Results

A total of nine studies from eight publications met the inclusion criteria and were included in this meta-analysis. Patient NOD2 SNPs were not associated with aGVHD risk. A tendency of higher risk to develop Grade III–IV aGVHD was found in patients with pairs NOD2 SNPs. Subgroup analyses showed that pairs NOD2 SNPs were associated with Grade III–IV aGVHD in the Caucasian population and in identical sibling donors (IS), but not in matched unrelated donors (MUD). In patients who received hematopoietic stem cell transplantation (HSCT) with T-cell depletion and gut decontamination, there was still an association between pairs NOD2 SNPs and Grade III–IV aGVHD risk.

Conclusions

Our meta-analysis suggests that pairs NOD2 SNPs, not patient NOD2 SNPs, may be associated with Grade III–IV aGVHD risk, especially in the Caucasian population. It is also indicated that in pairs NOD2 polymorphisms group, patients who receive HSCT from IS may experience higher risk of Grade III–IV aGVHD.     

Colorectal cancer and risk of atrial fibrillation and flutter: a population-based case–control study

Colorectal cancer has recently been associated with an increased atrial fibrillation risk, but evidence is very sparse. So, we conducted a population-based case-control study in northern Denmark (population 1.7 million) during 1998-2006 to estimate the atrial fibrillation/flutter risk in colorectal cancer patients. We identified 28,333 atrial fibrillation/flutter cases and 283,260 sex-, age-, and county-matched population controls. We searched the databases for a prior colorectal cancer diagnosis, a prior cancer diagnosis other than colorectal cancer, and performance of surgery within 30 days prior to atrial fibrillation/flutter. We used conditional logistic regression to estimate the OR of atrial fibrillation/flutter in patients with colorectal cancer, cancers other than colorectal and in patient with surgery. Among cases, 0.59% (n = 168) had a colorectal cancer diagnosis within 90 days before their atrial fibrillation/flutter diagnosis, compared with 0.05% (n = 155) of controls (adjusted OR = 11.8; 95% CI 9.3-14.9). Beyond the first 90 days after a colorectal cancer diagnosis, atrial fibrillation/flutter risk was no longer increased. There was likewise an increased atrial fibrillation/flutter risk in patients diagnosed with another cancer form in the prior 90 days (OR = 7.0, 95% CI 6.3-7.8). Furthermore, the atrial fibrillation/flutter risk was elevated fivefold in patients who had undergone surgery, whether or not cancer-related. We therefore conclude that colorectal cancer patients are at increased atrial fibrillation/flutter risk exclusively in the first 90 days after cancer diagnosis, but to no greater an extent than are patients with other cancers. The performance of surgery probably plays an important role in this association.     

The importance of −460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer

Purpose

The present study investigated the functional influence of the single nucleotide polymorphisms (SNPs) ?460 C/T and +405 G/C at vascular endothelial growth factor A (VEGF-A), mRNA and protein levels in colorectal cancer (CRC) and normal colorectal tissue.

Methods

Blood and tissue were collected from 113 patients surgically resected for colorectal cancer. SNPs were analysed from genomic DNA by PCR, the VEGF-A gene expression analysis was performed by RT–PCR and protein analysis by ELISA.

Results

The T-allele in the ?460 C/T SNP and the C-allele in the +405 G/C SNP were associated with significantly lower VEGF-A protein levels in normal colorectal tissue. There were no differences in protein levels in the malignant tissue according to genotypes. No differences were observed at the gene expression levels either.

Conclusion

The results indicate that the two SNPs have a functional influence on the VEGF-A protein levels in normal colorectal tissue. The possible clinical implications of the findings need further investigation.     

Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case–control study

Hippocampal brain regions are strongly implicated in Niemann Pick type C disease (NPC), but little is known regarding distinct subregions of the hippocampal complex and whether these are equally or differentially affected. To address this gap, we compared volumes of five hippocampal subfields between NPC and healthy individuals using MRI. To this end, 9 adult-onset NPC cases and 9 age- and gender-matched controls underwent a 3 T T1-weighted MRI scan. Gray matter volumes of the cornu ammonis (CA1, CA2 and CA3), dentate gyrus (DG), subiculum, entorhinal cortex and hippocampal-amygdalar transition area were calculated by integrating MRI-based image intensities with microscopically defined cytoarchitectonic probabilities. Compared to healthy controls, NPC patients showed smaller volumes of the CA1-3 and DG regions bilaterally, with the greatest difference localized to the left DG (Cohen’s d?=?1.993, p?=?0.008). No significant associations were shown between hippocampal subfield volumes and key clinical features of NPC, including disease duration, symptom severity and psychosis. The pattern of hippocampal subregional atrophy in NPC differs from those seen in other dementias, which may indicate unique cytoarchitectural vulnerabilities in this earlier-onset disorder. Future MRI studies of hippocampal subfields may clarify its potential as a biomarker of neurodegeneration in NPC.

     

The association of asthma and atrial fibrillation — A nationwide population-based nested case–control study

Background

Asthma and atrial fibrillation (AF) have been reported to be related to an increased risk of cardiovascular events. However, the relationship between asthma and AF has not been fully elucidated. The purpose of this study was to examine the association between asthma and AF risk.

Methods

We conducted a population-based nested case–control study including a total of 7439 newly-diagnosed adult patients with AF and 10,075 age-, gender-, comorbidity-, and cohort entry date-matched subjects without AF from the Taiwan National Health Insurance database. Exposure to asthma as well as medications including bronchodilators and corticosteroid before the index date was evaluated to investigate the association between AF and asthma as well as concurrent medications.

Results

AF patients were 1.2 times (adjusted OR 1.2, 95% CI 1.109–1.298) more likely to be associated with a future occurrence of asthma independent of comorbidities and treatment with corticosteroids and bronchodilator. In addition, the risks of new-onset AF were significantly higher among current users of inhaled corticosteroid, oral corticosteroids, and bronchodilators. Newly users (within 6 months) have the highest risk (inhaled corticosteroid: OR, 2.13; 95% CI, 1.226–3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P < 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P < 0.001). A graded association with AF risk was also observed among subjects treated with corticosteroid (inhaled and systemic administration) and bronchodilators. New users (within 6 months) of these medications had the highest risk of AF (ICS: OR, 2.13; 95% CI, 1.226–3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P < 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P < 0.001). A graded association with AF risk was also observed among subjects treated with ICS or bronchodilator.

Conclusions

Asthma was associated with an increased risk of developing future AF.     

Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, ?11377C>G, ?11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesis

The associations between adiponectin polymorphisms and type 2 diabetes have been studied widely; however, results are inconsistent.

Methods

We searched electronic literature databases and reference lists of relevant articles. A fixed or random effects model was used on the basis of heterogeneity. Sub-group and meta-regression analyses were conducted to explore the sources of heterogeneity.

Results

There were no statistically significant associations between +45T>G (rs2241766), +276G>T (rs1501299), ?11391G>A (rs17300539) and type 2 diabetes risk. However, for ?11377C>G (rs266729), the pooled OR (95% CI) for G vs C allele was 1.07 (1.03?C1.11, p?=?0.001). Subgroup analysis by study design revealed that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.0008) and G vs C allele (p?=?0.0004) might be associated with type 2 diabetes risk in population-based case?Ccontrol studies. After stratification by ethnicity, we found that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.004) and G vs C allele (p?=?0.001) might be associated with type 2 diabetes risk in white individuals. In individuals with a family history of diabetes, the presence of ?11391G>A (rs17300539) dominant model (GA+AA vs GG) and A vs G allele might be associated with increased risk of type 2 diabetes.

Conclusions/interpretation

The presence of +45T>G (rs2241766), +276G>T (rs1501299) and ?11391G>A (rs17300539) do not appear to influence the development of type 2 diabetes. However, G vs C allele of ?11377C>G (rs266729) might be a risk factor for type 2 diabetes.     

<Emphasis Type="Italic">CCND1</Emphasis> G870A polymorphism and cervical cancer risk: a case–control study and meta-analysis

Purpose  

Cyclin D1 (CCND1) is a key regulatory protein in the G1/S checkpoint of the cell cycle. We hypothesized that the G870A polymorphism of CCND1 is associated with the risk for cervical cancer and performed a meta-analysis of eligible studies to evaluate this relationship.     

Lack of association between XPD Lys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysis of case�Ccontrol studies

Purpose  

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and colorectal cancer remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship.     

Meta-analysis of the association between hOGG1 Ser326Cys polymorphism and risk of colorectal cancer based on case–control studies

Purpose

Oxidative DNA damage caused by reactive oxygen species plays an important role in cancer development. The association between colorectal cancer and hOGG1 Ser326Cys polymorphisms has been analyzed in several published studies, but mixed findings have been reported. The main purpose of this study was to integrate previous results and explore whether the polymorphism of hOGG1 is associated with susceptibility to colorectal cancer.

Methods

PubMed, Embase, Google Scholar, and Cbmdisc were searched for studies on the relationship of hOGG1 SNPs and the incidence of colorectal cancer (CRC). Eligible articles were included for data extraction. The main outcome was the frequency of hOGG1 Ser326Cys polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0.

Results

A total of 4,174 cases and 6,196 controls from 12 studies were included for this meta-analysis. Overall, stratified by ethnicity or population source, no significant associations between the hOGG1 Ser326Cys polymorphism and colorectal cancer risk were found for Cys/Cys allele (OR?=?1.146; 95?% CI: 0.978–1.342, P?=?0.091), Cys/Cys?+?Cys/Ser versus Ser/Ser (OR?=?1.045; 95?% CI: 0.975–1.121, P?=?0.213) Cys/Cys Versus Ser/Ser (OR?=?1.243; 95?% CI: 0.979–1.578, P?=?0.074) and Cys/Cys versus Cys/Ser?+?Ser/Ser (OR?=?1.198; 95?% CI: 0.959–1.496, P?=?0.111) in a recessive model and (OR?=?1.494; 95?% CI: 1.023–2.181, P?=?0.038) in a homozygote contrast. However, if apart from sensitivity analysis, there was some evidence to indicate that significantly increased risks were found among European plus American subjects, who are mostly Caucasian (OR?=?1.444; 95?% CI: 1.017–2.05 Cys/Cys vs. Ser/Cys?+?Ser/Ser; P?=?0.04). In the subgroup analyses, we also did not found any association between hOGG1 Ser326Cys polymorphism and certain populations and smokers.

Conclusions

This meta-analysis suggests that there is no robust association between hOGG1 Ser326Cys polymorphism and colorectal cancer. Because of the limitation of meta-analysis, this finding demands further investigation.     

Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population

Purpose

Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene–gene and gene–environment in a case–control study of an Indian population.

Methods

This case–control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR–RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression.

Results

The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04–2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46–1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43–9.44).

Conclusions

The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.     

MDR1 gene C3435T polymorphism and cancer risk: a meta-analysis of 34 case–control studies

Background

P-glycoprotein, the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of environmental toxins and xenobiotics. Epidemiological studies have evaluated the association between MDR1 C3435T polymorphism and cancer susceptibility. However, published data are still inconclusive.

Methods

To derive a more precise assessment of this relevance, we performed a meta-analysis, up to September 2010, of 5,196 cases with different cancer types and 6,827 controls from 34 published case–control studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for MDR1 C3435T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate.

Results

The overall results suggested that the variant was associated with a moderately increased cancer risk in all comparison models tested (OR?=?1.26, 95% CI: 1.06–1.50 for TT vs. CC; OR?=?1.19, 95% CI: 1.04–1.37 for CT vs. CC; OR?=?1.15, 95% CI: 1.01–1.32 for recessive model; OR?=?1.21, 95% CI: 1.06–1.38 for domain model, and OR?=?1.14, 95% CI: 1.04–1.26 for allele contrast). In the subgroup analysis by cancer types, significant associations were found in breast cancer (OR?=?1.66, 95% CI: 1.24–2.21 for TT vs. CC; OR?=?1.44, 95% CI: 1.14–1.82 for recessive model; OR?=?1.41, 95% CI: 1.10–1.81 for domain model; and OR?=?1.31, 95% CI: 1.13–1.52 for allele contrast) and renal cancer (OR?=?1.99, 95% CI: 1.37–2.90 for TT vs. CC; OR?=?1.74, 95% CI: 1.25–2.42 for domain model; OR?=?1.43, 95% CI: 1.09–1.88 for recessive model; and OR?=?1.40, 95% CI: 1.17–1.68 for allele contrast). However, no significant associations were found in colorectal cancer, gastric cancer, and acute lymphoblastic leukemia for all genetic models. In the ethnicity subgroup analysis, a significant association with cancer among Caucasians was found under the dominant model, homozygote comparison, CT versus CC comparison, and allele comparison.

Conclusions

In summary, this meta-analysis suggests that the MDR1 C3435T polymorphism is associated with cancer susceptibility, increasing the risk of breast and renal cancer.