Case-control Study In Chinese Population Research Articles

The relationship between epicardial adipose tissue volume on coronary computed tomography angiography and idiopathic ventricular tachycardia: a propensity score matching case-control study in Chinese population.

Large epicardial adipose tissue (EAT) volume is associated with the incidence of premature ventricular beats. The relationship between EAT volume and idiopathic ventricular tachycardia (IVT) is not yet clear. We aimed to investigate the effect of EAT volume on the risk of IVT. This is a retrospective consecutive case-control study from January 2020 to September 2022. IVT patients (n=81) and control patients (n=162) undergoing coronary computed tomography angiography (CCTA) were retrospectively recruited. The patients in the control group were all hospitalized patients for different reasons, such as chest tightness, shortness of breath, chest pain, and so on. Demographic parameters and clinical characteristics of each individual were collected from the patient's medical records. We selected evaluation criteria for the conduct of a 1:1 propensity score (PS)-adjusted analysis. Multivariable logistic analysis was used to investigate risk factors for IVT. Furthermore, the impact of EAT volume on cardiac repolarization indices was assessed in IVT patients. Patients with IVT had a larger EAT volume than control group patients in the unadjusted cohort. Variables with P<0.10 in the univariable analysis and important factors were included in the multivariable analysis model, including body mass index (BMI), left ventricular ejection fraction (LVEF), early peak/artial peak (E/A) ratios <1, EAT attenuation, and EAT volume (per increase 10 mL). The multivariable logistic analysis found that EAT volume [per increase 10 mL, odds ratio (OR): 1.29, 95% confidence interval (CI): 1.17-1.41, P<0.001] was an independent risk factor for IVT. EAT volume (per increase 10 mL, OR: 1.43, 95% CI: 1.25-1.64, P<0.001) independent effect was demonstrated in the PS adjusted cohort (n=57 in both groups). The area under the curve of EAT volume to predict the risk of IVT patients in the PS adjusted cohort was 0.859. The sensitivity and specificity were 86.0%, and 75.4%, respectively. Furthermore, A large EAT volume of IVT patients had a longer time in Tp-e, and Tp-e/QTc, compared with low EAT volume. Patients with IVT had increased EAT volume compared to control subjects. Our study revealed that large EAT volume is associated with an extended repolarization process in IVT patients. These insights are essential for understanding the mechanisms linking EAT with IVT.

Neuregulin 1 as a potential biomarker for disease progression in moyamoya disease: A case-control study in Chinese population

ObjectiveMoyamoya disease (MMD) is a rare and progressive stenosis of cerebral arteries characterized by abnormally proliferative vasculopathy. Current studies have demonstrated that Neuregulin 1 (NRG1) plays a key role in angiogenesis-related disorders. Thus, the aim of our study is to investigate the serum NRG1 levels and their clinical correlations in MMD patients. MethodsIn this study, thirty adult patients with MMD and age-gender matched healthy controls were enrolled from our hospital between July 2020 and April 2022. Peripheral blood samples were collected at baseline, and clinical data were obtained from the electronic medical record system. Serum NRG1 concentrations were measured by enzyme-linked immunosorbent assay. Sanger sequencing was applied to detect the RNF213 p.R4810K mutation. ResultsThe serum NRG1 levels were significantly higher in MMD patients compared to controls (14.48 ± 10.81 vs.7.54 ± 6.35mmol/L, p < 0.001). No statistical difference in baseline clinical characteristics was found between both groups. Correlation analyses showed that NRG1 levels were positively associated with Suzuki staging (r = 0.4137, p = 0.023) while not related to other clinical features (reduced cerebral blood flow, posterior cerebral artery involvement, bilateral or unilateral steno-occlusive changes). Furthermore, subgroup analysis revealed that MMD patients with the RNF213 p.R4810K mutation presented with significantly higher NRG1 levels than those without the mutation (9.60 ± 0.929 vs. 25.89 ± 4.338 mmol/L, p = 0.001). ConclusionsOur study suggests that increased serum NRG1 levels may constitute a characteristic feature of MMD, indicating a potential positive correlation with disease progression and the presence of the RNF213 mutation. This positions NRG1 as a potentially crucial target for further studies aimed at comprehending the pathogenesis of MMD.

Association of IL13 polymorphisms with susceptibility to myocardial infarction: A case-control study in Chinese population.

Inflammatory cytokines play a major role in the pathogenesis of myocardial infarction (MI). Although information on the importance of interleukin 13 (IL13) in human MI is limited, it has been well documented in the mouse model. Genetic variation in the IL13 gene has been associated with the structure and expression of the IL13. In the present study, we hypothesized that IL13 common genetic variants would be associated with a predisposition to the development of MI. The present study enrolled 305 MI patients and 310 matched healthy controls. Common genetic polymorphisms in the IL13 gene (rs20541, rs1881457, and rs1800925) were genotyped using the TaqMan SNP genotyping method. Plasma levels of IL13 were measured using an enzyme-linked immunosorbent assay (ELISA). In MI patients, minor alleles of the IL13 rs1881457 and rs1800925 polymorphisms were less common than in healthy controls [rs1881457: AC (P = 0.004, OR = 0.61), C (P = 0.001, OR = 0.66); rs1800925: CT (P = 0.006, OR = 0.59)]. Further haplotype analysis of three studied SNPs revealed a significant association with predisposition to MI. Interestingly, IL13 rs1881457 and rs1800925 were linked to plasma levels of IL13: the reference genotype had higher levels, heterozygotes were intermediate, and the alternate genotype had the lowest levels. In the Chinese population, IL13 (rs1881457 and rs180092) variants are associated with different plasma IL13 levels and offer protection against MI development. However, additional research is required to validate our findings in different populations, including descent samples.

Breast adipose metabolites mediates the association of tetrabromobisphenol a with breast cancer: A case-control study in Chinese population

Studies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population.

BackgroundPrevious studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways.MethodsThe concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified.ResultsThe concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74–0.85]) in the training data set and 0.79 (95%CI [0.71–0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68–0.81]) and 0.86 (95% CI [0.82–0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85–0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71–0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis.ConclusionsThe levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.

FYB methylation in peripheral blood as a potential marker for the early-stage lung cancer: a case-control study in Chinese population

Background Lung cancer (LC) is the leading cause of cancer-related morbidity and mortality in China. Exploring novel biomarkers for the early detection of LC is important. Materials and methods We quantified DNA methylation levels of three CpG sites of FYB gene in peripheral blood in 163 early-stage LC cases (88.3% at stage I) and 187 age- and gender-matched healthy controls. Covariates-adjusted odds ratios (ORs) for −10% methylation were calculated by binary logistic regression. Results With multiple testing corrections, hypomethylation of FYB_CpG_4 was significantly associated with LC (OR = 2.04, p = 4.50E-04) even with LC at stage I (OR = 1.41, p = 0.003) without obvious bias between genders, but it mainly affected the subjects older than 55 years (OR = 2.04, p = 0.015). Hypomethylation of FYB_CpG_2 was also associated with LC, but only for the males (OR = 1.76, p = 0.018). FYB_CpG_3 methylation had no association with LC, but interestingly its methylation level in the males was only half of that in the females. Discussion and conclusions We proposed a novel association between blood-based abnormal FYB methylation and very early-stage LC. The age- and gender-related DNA methylation patterns also revealed the diversity and precision of epigenetic regulations.

Serum Cystatin C as a Potential Predictor of the Severity of Multiple System Atrophy With Predominant Cerebellar Ataxia: A Case-Control Study in Chinese Population

Objective: Multiple system atrophy (MSA) is a serious neurodegenerative disease that is charactered by progressive neurological disability. The aim of this study was to investigate the correlation of serum oxidant factors with the severity of MSA.Methods: A total of 52 MSA patients and 52 age- and gender- matched healthy subjects were retrospectively enrolled in this study. Enzymatic colorimetric methods were used to assay the concentrations of uric acid (UA), serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C (Cys-C). Disease severity was evaluated by the Unified Multiple System Atrophy Rating Scale (UMSARS). The disease progression rate was defined by the change in UMSARS-IV (global disability score, GDS) over a 1-year period.Results: Comparisons between the two groups revealed that there were no significant differences in terms of serum Scr (70.81 ± 13.88 vs. 70.92 ± 14.19 μmol/L, p = 0.967). However, the serum levels of the other three biomarkers were significantly higher in the MSA patients (UA: 325.31 ± 84.92 vs. 291.19 ± 64.14 μmol/L, p = 0.023; BUN: 5.68 ± 1.67 vs. 4.60 ± 1.24 mmol/L, p < 0.001; Cys-C: 0.96 ± 0.15 vs. 0.89 ± 0.14 mg/L, p = 0.024). In addition, Pearson correlation analyses revealed that only serum Cys-C was significantly correlated to GDS (r = 0.281, p = 0.044). Subgroup analysis further demonstrated that serum Cys-C was the only factor that was positively associated with the disease severity in patients with MSA and predominant cerebellar ataxia (MSA-C) (r = 0.444, p = 0.018); there was no significant association in MSA patients with predominant Parkinsonism (MSA-P) (r = 0.118, p = 0.582). MSA-C patients with severe disability were shown to express higher serum levels of Cys-C than patients with mild disability (1.03 ± 0.13 vs. 0.88 ± 0.12 mg/L, p = 0.009). Finally, Kaplan-Meier plots revealed a significant difference in the 5-year probability of survival from severe disability between MSA-C patients with high- and low-concentrations of serum Cys-C (Log-rank test: X2 = 4.154, p = 0.042). ROC curve analysis confirmed that serum Cys-C exhibits good performance as a biomarker (AUC = 0.847).Conclusion: Our research indicated that oxidative stress plays a vital role in MSA. Serum Cys-C represents a potential prognostic biomarker to evaluate the severity of disease in patients with MSA-C.

Identification of genetic variants in m6A modification genes associated with pancreatic cancer risk in the Chinese population.

N6-Methyladenosine (m6A) is the most prevalent modification of RNA in eukaryotes, and is associated with many cellular processes and even the development of cancers. We hypothesized that single-nucleotide polymorphisms (SNPs) in m6A modification genes, including its "writers", "erasers" and "readers", might affect the m6A functions and associate with the susceptibility to pancreatic ductal adenocarcinoma (PDAC). We first conducted a two-stage case-control study in Chinese population to interrogate all SNPs in 22 m6A modification genes. In the discovery stage, a total of 2735 SNPs were genotyped in 980 patients and 1991 controls. Then, the promising SNP was replicated in another independent population consisting of 858 cases and 2084 controls. As a result, we found the rs7495 in 3'UTR of hnRNPC was significantly associated with increased risk of PDAC in both stages (combined odds ratio = 1.22, 95% confidence interval = 1.12-1.32, P = 2.39 × 10-6). To further reveal the biological function of rs7495 and hnRNPC, we performed a series of biochemical experiments. Luciferase reporter assays indicated that rs7495G allele promoted hnRNPC expression through disrupting a putative binding site for has-miR-183-3p. Cell viability assay demonstrated that knockdown of hnRNPC suppressed the proliferation of PDAC cells. RNA-seq analysis suggested that as an m6A "reader", hnRNPC played an important role in RNA biological processes. In conclusion, our findings elucidated that rs7495G could confer higher risk of PDAC via promoting the expression of hnRNPC through a miRNA-mediated manner. These results provided a novel insight into the critical role of m6A modification in tumorigenesis.

Association of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 polymorphisms with systemic lupus erythematosus disease activity and biomarker levels: A case-control study in Chinese population.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with considerable genetic predisposition. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) is crucial for the innate immunity and implicated in SLE pathogenesis. Accordingly, we conducted a case-control study to find the association of NLRP3 variations with SLE susceptibility and disease activity.Three single nucleotide polymorphisms of NLRP3 (rs3806268, rs4612666, and rs10754558) were genotyped in 400 SLE patients and 400 healthy controls; the patients were further divided into mild-to-moderate or high disease activity subgroup. Serum cytokines, complements, and autoantibodies were also detected.We found that rs4612666 TT genotype conferred a higher risk of severe disease activity with adjusted odds ratio = 2.08, P = .02 and adjusted odds ratio = 2.34, P = .01 in the codominant and recessive model, respectively. Nevertheless, there was no association between the 3 single nucleotide polymorphisms of NLRP3 gene and SLE susceptibility. In addition, C4 decreased significantly in rs3806268 GG (P < .001) and rs4612666 TT genotype carriers (P = .03). A higher trend of interleukin-1β and interleukin-γ release were identified in rs3806268 AA and rs10754558 CC genotype carriers, respectively.NLRP3 polymorphisms are associated with SLE disease activity and hypocomplementemia. Interleukin-1β and interleukin-γ levels in SLE patients are correlated with NLRP3 variants as well.

Urinary bisphenol A and its interaction with ESR1 genetic polymorphism associated with non-small cell lung cancer: findings from a case-control study in Chinese population

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 μg/L, P < 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39–2.62, P < 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1.

An HLA class II locus, previously identified by a genome-wide association study, is also associated with susceptibility to pulmonary tuberculosis in a Chinese population

ObjectiveGenome-wide association study (GWAS) in Icelanders identified HLA class II sequence variants on chromosome 6p21 as tuberculosis (TB) susceptibility loci. To evaluate the role of these loci in other populations with different ancestry, we conducted a case-control study in Chinese population. MethodsWe genotyped two genetic variants (rs9272461 and rs9271300) on the reported chromosome 6p21 in 739 pulmonary tuberculosis (PTB) cases and 749 healthy controls from Chinese Han population using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate the association between genetic variants and PTB risk and to estimate corresponding odds ratios (ORs) and 95% confidence intervals (95%CIs). ResultsWe found that rs9272461 was significantly associated with the risk of PTB in various genetic models (dominant OR = 0.75, 95%CI: 0.61–0.92; recessive OR = 0.64, 95%CI: 0.46–0.90, and additive OR = 0.78, 95%CI: 0.67–0.90). Moreover, in the stratified analysis in additive model, the association was also significant in the old (age ≥ 48 years) (OR = 0.76, 95%CI: 0.62–0.93; P = .008), men (OR = 0.71, 95%CI: 0.59–0.85; P < .001), and new PTB cases (OR = 0.76, 95%CI: 0.65–0.90; P = .001). The association results were similar between the microbiologically negative (OR = 0.78, 95%CI: 0.64–0.94; P = .008) and positive cases (OR = 0.77, 95%CI: 0.64–0.93; P = .008). We did not observe significant association for rs9271300 neither in the overall analysis (additive model: OR = 0.98, 95%CI: 0.85–1.13; P = .776) nor in the stratified analysis. ConclusionsOur findings indicate that the HLA class II locus also affects the susceptibility to PTB in Chinese population. Further validation studies and function experiments are required to confirm the roles of the discovered variant.

Association between genetic variants in p53 binding sites and risks of osteosarcoma in a Chinese population: a two-stage case-control study

Osteosarcoma (OS) is one of the most common bone malignancies in children and adolescents. To date, inaugural mechanism of OS was considered as a complex process and was still not clear. The p53 gene, most important tumor suppressors, was associated with risk of many tumors, including OS. In current study, we evaluated the relationship between genetic variation of the p53 binding site and the OS susceptibility through a two-stage case-control study in Chinese population. We found that rs1295925 (OR = 0.85; 95 CI = 0.76-0.94; P = 0.003) and rs3787547 (OR = 1.27; 95 CI = 1.11-1.45; P = 4.0 × 10−4) was significantly with OS susceptibility. Compared with those with rs1295925-TT genotype, and the risk of OS was significantly lower in individuals with CT genotype (OR = 0.77; 95 CI = 0.65-0.92) and CC genotype (OR = 0.75; 95 CI = 0.60-0.93). Compared with those with rs3787547-GG genotype, and the risk of OS was significantly higher in individuals with AG genotype (OR = 1.32; 95 CI = 1.10-1.58) and AA genotype (OR = 1.46; 95 CI = 1.11-1.92). To sum up, our results prove that SNP rs1295925 and rs3787547 play an important role in the etiology of OS, suggesting them as the potential genetic modifier for OS development.

Genetic variations in chromodomain helicase DNA-binding protein 5, gene-environment interactions and risk of sporadic Alzheimer's disease in Chinese population.

CHD5 is an essential factor for neuronal differentiation and neurodegenerative diseases. Here, the targeted next generation sequencing and TaqMan genotyping technologies were carried out for CHD5 gene in a two-staged case-control study in Chinese population. The genetic statistics and gene-environment interactions were analyzed to find certain risk factors of Alzheimer's disease. We found intronic rs11121295 was associated with the risk of Alzheimer's disease at both stages including combined cohorts. This risk effect presented consistently significant associations with the alcoholic subgroups at both all stages in the stratified analysis. The gene-environment interactions further supported the above findings. Our study highlighted the potential role of CHD5 variants in conferring susceptibility to sporadic Alzheimer's disease, especially modified its risk by alcoholic intake.

Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal liver function: a case-control study of Chinese population

Context: Acute or chronic exposure of N,N-dimethylacetamide (DMAc) is responsible for abnormal liver function. It appears that DMAc is mainly metabolized by cytochrome P450 in the liver and thereby produces reactive oxygen species (ROS). The elimination of ROS and the repairing of ROS-induced DNA damage are relevant to the ultimate toxicity of DMAc.Objective: To investigate whether the polymorphisms in the CAT (rs564250, rs769214 and rs7943316), hOGG1 (rs2072668 and rs159153) and XRCC1 (rs25487 and rs1799782) genes are associated with susceptibility to DMAc-induced abnormal liver function in Chinese population.Methods: Samples were obtained from 108 workers with DMAc-induced abnormal liver function and 108 workers with normal liver function.Results: Subjects with the CAT rs769214 GA/GG genotypes had a reducing risk of abnormal liver function, which was more evident in the subgroups exposed to DMAc <10 years, exposed to DMAc <5 mg/m3, never smoked and never drank.Conclusions: CAT rs769214 (-844 G > A) polymorphism may be associated with DMAc-induced abnormal liver function in Chinese population.

Relationship between Alzheimer's disease GWAS-linked top hits and risk of Parkinson's disease with or without cognitive decline: a Chinese population-based study

Alzheimer's disease (AD), Parkinson's disease (PD), and cognitive impairment in PD have overlapping clinical and pathological features. To examine whether there is a genetic link for these diseases, we performed a case-control study in Chinese population to evaluate the association of AD genome-wide association studies top hits with both PD and cognitive function in PD, investigating 13 single-nucleotide polymorphisms in 9 genes (BIN1, CLU, ABCA7, CR1, PICALM, MS4A6A, CD33, MS4A4E, and CD2AP). A total of 454 controls and 442 PD patients were genotyped, including 75 mild cognitive impairment and 99 dementia. As a result, no significant association of the AD-susceptibility loci was identified in PD cases, PD–dementia, or PD–mild cognitive impairment. Our findings imply that the 13 single-nucleotide polymorphisms from AD genome-wide association studies may not play major role in the genetic predisposition with PD and cognitive function in PD in a Chinese population.

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population.

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TLSNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P < 0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P < 0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84-3.14), 1.36 (1.03-1.79), 1.01 (0.76-1.35), and 1.37 (1.03-1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

Incidence and Risk of Cardiotoxicity Induced by Sunitinib in Patients with Renal Cell Carcinoma: A Population-Based Case-Control Study in Chinese Population.

Incidence and Risk of Cardiotoxicity Induced by Sunitinib in Patients with Renal Cell Carcinoma: A Population-Based Case-Control Study in Chinese Population.

Abstract LB-289: Telomere length, genetic variants and gastroesophageal cancer risk: a case-control study in Chinese population

Abstract Backgrounds Telomeres are protective DNA-protein repeats structure at the extreme end of linear chromosomes that maintain chromosomal stability and integrity. Short telomere in peripheral blood leukocyte has been associated with an increased risk of multiple cancers. Moreover, heterogeneity of inter-individual telomere length is partly determined by hereditary factor. Recent genome-wide association studies (GWAS) have identified several telomere length related loci at 2p16.2 (ACYP2), 3q26 (TERC), 4q32.2 (NAF1), 5p15.33 (TERT), 10q24.33 (OBFC1), 19p12 (ZNF208) and 20q13.3 (RTEL1), some of which were also implicated with cancer risk. However, these findings were mainly observed in populations of European descent, and were not well demonstrated in other populations, especially for gastroesophageal cancer that is high incident in China but not in western countries. Design and Methods We measured relative telomere length (RTL) by quantitative real-time polymerase chain reaction in a Chinese case-control study including 1,136 gastric cancer cases, 1,045 esophageal cancer cases and 1,012 matched controls. Moreover, we performed genotyping by TaqMan assay for genetic variants at 2p16.2 (rs11125529), 3q26 (rs10936599), 4q32.2 (rs7675998), 5p15.33 (rs2736100, rs2736108), 10q24.33 (rs4387287), 19p12 (rs8105767), and 20q13.3 (rs755017). Results As compared with individuals in the fourth quintile of telomere length (i.e., moderately long telomeres), those with short telomeres were at an increased risk with ORs (95%CI) being 1.19 (0.92-1.55), 1.53 (1.19-1.98) and 3.00 (2.33-3.85) for the third, second and first quintiles, respectively. More interestingly, a significant elevated risk (OR= 1.54, 95%CI: 1.19-2.00) was also found in those at the fifth quintile with extreme long telomeres. We also confirmed that the G allele of rs2736100 at 5p15.33 exhibited a significant association with longer telomere length (r2= 0.106, P = 0.047), which, however, was not significantly associated with gastroesophageal cancer risk. We did not observe significant association of the other loci with telomere length or gastroesophageal cancer risk. Conclusions These findings suggest that either short or extreme long telomere may be risk factor for gastroesophageal cancer while telomere length related variants may be less important in the susceptibility to gastroesophageal cancer in Chinese population. Citation Format: Jiangbo Du, Xun Zhu, Chen Zhu, Hongxia Ma, Zhibin Hu, Hongbing Shen, Guangfu Jin. Telomere length, genetic variants and gastroesophageal cancer risk: a case-control study in Chinese population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-289. doi:10.1158/1538-7445.AM2014-LB-289

Genetic variant in SWI/SNF complexes influences hepatocellular carcinoma risk: a new clue for the contribution of chromatin remodeling in carcinogenesis

Chromatin remodeling has been newly established as an important cancer genome characterization and recent exome and whole-genome sequencing studies of hepatocellular carcinoma (HCC) showed that recurrent inactivating mutations in SWI/SNF subunits involved in the molecular basis of hepatocarcinogenesis. To test the hypothesis that genetic variants in the key subunits of SWI/SNF complexes may contribute to HCC susceptibility, we systematically assessed associations of genetic variants in SWI/SNF complexes with HCC risk using a two-staged case-control study in Chinese population. A set of 24 single nucleotide polymorphisms (SNPs) in SWI/SNF complexes were examined in stage 1 with 502 HCC patients and 487 controls and three promising SNPs (SMARCA4 rs11879293, rs2072382 and SMARCB1 rs2267032) were further genotyped in stage 2 comprising 501 cases and 545 controls for validation. SMARCA4 rs11879293 presented consistently significant associations with the risk of HCC at both stages, with an OR of 0.73 (95% CI: 0.62–0.87) using additive model in combined analysis. Moreover, the decreased risk of HCC associated with SMARCA4 rs11879293 AG/AA was more evident among HBsAg positive individuals (OR = 0.47, 95% CI: 0.27–0.80) in combined analysis. The study highlighted the potential role of the SWI/SNF complexes in conferring susceptibility to HCC, especially modified HCC risk by HBV infection.

PCN10 Risk of Breast Cancer and Statins: A Population-Based Nested Case-Control Study in Chinese Population

PCN10 Risk of Breast Cancer and Statins: A Population-Based Nested Case-Control Study in Chinese Population