Carcinoma In Chinese Han Population Research Articles

Single nucleotide polymorphism within gene in NFKBIA is associated with the risks of nasopharyngeal carcinoma in Chinese Han population.

67 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs (Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs that we found were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.

Association between polymorphism of the cyclin E1 gene and susceptibility to hepatocellular carcinoma in Chinese Han population of Hubei

This study aimed to explore the relationship between CCNE1 gene single nucleotide polymorphisms (SNP rs1406 and rs3218038) and the incidence of hepatitis B virus-related hepatocellular carcinoma (HCC) in the Chinese Han population in Hubei. A total of 663 subjects, including 173 HCC patients, 172 HBV-related liver cirrhosis (LC) patients, 162 asymptomatic HBV carriers (AsC), and 156 healthy controls, participated in the study. Genotyping of CCNE1 rs1406 and rs3218038 polymorphisms was done by illumina second generation sequence method.Our findings showed that rs1406 G>T variant decreased the risk of HCC (OR 0.710, P=0.035 G vs T), and no significant differences were found between rs3218038 SNP and HCC risk using the χ² test. Furthermore, stratified analysis revealed that differences in genotype frequencies were related to gender. Women who carried the CCNE1 GT genotype were significantly associated with a decreased risk of HCC, compared with healthy controls carrying the GG genotype (additive model, OR 0.378,P=0.030).The results suggest that the rs1406 G allele and CCNE1 rs1406 polymorphism produce an increased the risk of HCC in comparison with the T allele. Whereas, the GT genotype is a protective factor in the development of HCC in female patients.

The Impact of IL-16 3'UTR Polymorphism rs859 on Lung Carcinoma Susceptibility among Chinese Han Individuals.

Lung carcinoma is the most common cancer and cause of cancer deaths among both males and females in China. Previously, genetic variants located in gene untranslated region have been well established as interfering factors in mRNA translation and confirmed playing critical roles in lung oncogenesis. However, the correlation between polymorphisms in gene 3′ untranslated region and lung cancer risk is less reported in China Han population. In this study, polymorphisms in 3′-untranslated region of IL-16, CYP24A1, and FBN1 were determined in 322 lung cancer patients and 384 healthy controls with the usage of Sequenom MassARRAY. The correlation between selected variants and lung cancer risk was examined by unconditional logistic regression analysis with or without adjustments for age, gender, smoking status, and alcohol drinking status. Additionally, stratification analysis was applied to detect the associations of SNPs with lung cancer in different subgroups. As the results, significant relationships were found between IL-16 rs859 and lung cancer susceptibility in recessive model (OR= 0.65, 95% CI: 0.44-0.96, P= 0.029) and log-additive model (OR= 0.76, 95% CI: 0.60-0.96, P= 0.019). Moreover, adjusted stratified analysis also revealed the important effects of IL-16 rs859 on lung cancer risk among individuals aged older than 50, males, and nondrinkers. IL-16 rs859 showed statistically significant evidence associated with susceptibility to lung adenocarcinoma and lung small cell carcinoma in Chinese Han population as well. Our research demonstrated that genetic variant rs859 of IL-16 3′UTR was associated with lung cancer risk in Chinese Han population and the result might be exploited as a new biomarker for lung cancer assessment and prevention.

Association Between Polymorphisms in the Promoter Region of microRNA-34b/c and the Chemoradiotherapy Efficacy for Locally Advanced Esophageal Squamous Cell Carcinoma in Chinese Han Population.

The study aims to explore the association between polymorphisms in the promoter region of microRNA-34b/c (miR-34b/c) and the chemoradiotherapy efficacy for locally advanced esophageal squamous cell carcinoma (ESCC) in Chinese Han population. A total of 175 locally advanced ESCC cases and 186 healthy individuals were enrolled as the case and control groups. Denaturing high performance liquid chromatography (DHPLC) was applied to determine the genotypes of subjects. Subjects in the case group were classified into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR + PR were defined as the sensitive group, and SD + PD were defined as the resistance group. All patients were followed up for 3 ~ 36months. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of rs4938723 in the promoter region of miR-34b/c in the chemoradiotherapy efficacy for patients with locally advanced ESCC. The distribution of genotype and allele of rs4938723 in the promoter region of miR-34b/c was significantly different between the case and control group (both P < 0.05), and CC genotype and C allele could decrease the risk of ESCC (CC genotype: OR = 0.57, 95%CI = 0.32 ~ 0.99, P = 0.045; C allele: OR = 0.72, 95%CI = 0.54 ~ 0.97, P = 0.032). MiR-34b/c rs4938723 was associated with ESCC TNM staging, differentiation degree, and lymph node metastasis (LNM) for ES CC patients (all P < 0.05). The chemoradiotherapy efficacy of patients with CC genotype was better than that of patients with (TT + TC) genotypes (P < 0.05). ROC curve results showed that the area under curve (AUC), sensitivity and specificity were 0.777, 85.1% and 71.3%, respectively. The average median progression free survival (PFS) of patients with (TT + TC) genotypes was significantly shorter than those patients with CC genotype (P < 0.05). Our study provides evidence that miR-34b/c rs4938723 is closely related with the chemoradiotherapy efficacy for locally advanced ESCC.

IL1 genes polymorphism and the risk of renal cell carcinoma in Chinese Han population.

Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. However, with the lack of diagnostic screening biomarkers, early diagnosis of RCC is challenging. Our study was investigated the association of IL1 gene polymorphisms and RCC risk. We conducted a case-control study of 291 RCC cases and 463 controls to evaluation the IL1RN of single nucleotide polymorphisms (SNPs) on RCC risk. We selection of 16 SNPs in IL1RN, IL1A, IL1B genes were analyzed. Using the chi-squared (χ2) test and genetic model analysis, we found an association with RCC risk for five SNPs [rs3783550 (IL1A), rs3783546 (IL1A), rs1609682 (IL1A), rs3783521 (IL1A), and rs1143623 (IL1B)] and increased the risk of RCC. Stratified analyses show that smoking, not drinking and age>55 populations relative to nonsmoking, drinking and age<55 more susceptible. Our study suggested that IL1B and IL1A may involve in the development of RCC in Chinese Han population.

Associations between polymorphisms in the IL-4 gene and renal cell carcinoma in Chinese Han population.

Renal cell carcinoma (RCC) is considered to be a kind of cytokine reactive tumor. The research has been suggested that the host immune system can regulate the clinical course of RCC. Therefore, cytokine gene polymorphisms in RCC patients were analyzed was necessary. Our study is purpose to analyzing the interleukin-4(IL-4) polymorphisms associated with RCC risk from Han Chinese population. IL-4 genetic polymorphisms were genotyped using Massarray technology from a total of 291RCC and 463 controls. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. A significant association was found between the rs2243250 “C” allel and decreased risk of RCC (OR=0.75, 95%CI=0.59-0.96, P=0.02). Stratified analysis based on the age, gender, smoking status, drinking status revealed no significant association with RCC in age>55, female, smoking and nodrinking. However, for age<55 group (rs2243250, rs2243267, rs2243270), male group (rs2243250), nonsmoking group (rs2227284), and drinking group (rs2243250, rs2227284, rs2243267, rs2243270) polymorphisms were found obviously associated with RCC. The haplotype analyses showed that the haplotype have a significant decreased risk of RCC in the rs2243250/rs2227284/rs2243267/rs2243270/rs2243283/rs2243289 (CGGACA) (Total, OR=0.73, 95%CI=0.54-0.98, P=0.034; Male, OR=0.59, 95%CI=0.39-0.90, P=0.014). Therefore, the present study suggests that IL-4 may be a candidate gene for assessing the risk of RCC.

Leukocyte telomere length-related genetic variants in ACYP2 contribute to the risk of esophageal carcinoma in Chinese Han population.

BackgroundShort leukocyte telomere length has been associated with significantly increased risk of esophageal carcinoma. A previous genome-wide association study demonstrated that ACYP2 was associated with leukocyte telomere length. However, the role of ACYP2 genetic variants on esophageal carcinoma susceptibility is still unknown. Therefore, we investigated whether ACYP2 polymorphisms have impact on the risk of esophageal carcinoma in Chinese.Materials and MethodsWe conducted a case-control study among 386 cases and 495 healthy controls from northwest China. 14 SNPs in ACYP2 were selected and genotyped using Sequenom MassARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and gender.RESULTSWe found that 1.34-fold increased risk of esophageal carcinoma is associated with the rs11125529 A allele compared with the rs11125529 C allele (OR=1.29, 95%CI: 1.02-1.62, p=0.030) under the additive model, after adjusted by age and gender. We also found rs11896604 and rs17045754 loci increased the esophageal carcinoma risk under the additive model (rs11896604: OR=1.34, 95%CI: 1.03-1.76, p=0.032; rs17045754: OR=1.36, 95%CI: 1.03-1.80, p=0.028). One main linkage block was observed across the locus. This block was comprised of seven closely linked SNPs: rs1682111, rs843752, rs10439478, rs843645, rs11125529, rs843711 and rs11896604. The haplotype analysis detected that haplotype “TTCTATG” increased the risk of esophageal carcinoma (OR=1.38, 95%CI: 1.04-1.82, p=0.025).ConclusionIn conclusion, ACYP2 gene may be associated with an increased risk of esophageal carcinoma in Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of esophageal carcinoma are warranted.

Association of genetic polymorphisms in PTEN and additional gene-gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population.

This study aims to investigate the association of five single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homologue (PTEN) gene and additional role of gene-gene interaction with esophageal squamous cell carcinoma (ESCC), based on a Chinese case-control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case-control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio (OR) and 95% confident interval (95%CI) were calculated. All genotypes were distributed according to Hardy-Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild-type homozygotes, and OR (95%CI) were 1.27 (1.09-2.08) and 1.45 (1.17-1.98), respectively. We also found a potential gene-gene interaction between rs2735343 and rs701848 (P = 0.0010), and a potential gene-gene interaction among all five SNP (P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37-3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene-gene interaction between rs2735343 and rs701848 and a potential gene-gene interaction among all five SNPs.

Genetic variants in miR-196a2 and miR-499 are associated with susceptibility to esophageal squamous cell carcinoma in Chinese Han population

Esophageal squamous cell carcinoma (ESCC) is the dominant type of esophageal cancer in the East Asian population. MicroRNAs (miRNAs) have been studied to play important roles in tumorigenesis. Single nucleotide polymorphisms (SNPs) in miRNA lead to the aberrant expression and structural alteration of miRNA and are hypothesized to be involved in tumorigenesis and cancer development. We conducted a population-based case-control study to evaluate the association between SNPs in miRNAs and ESCC risk in 1400 ESCC cases and 2185 matched controls. Four SNPs including miR-196a2 rs11614913, miR-146a rs2910164, miR-499 rs3746444, and miR-423 rs6505162 were selected with comprehensive collection strategy and genotyped using the SNaPshot Multiplex System. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of association. The CC genotype of miR-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype (OR 1.11, 95% CI 1.01-1.22, P 0.049) and the TT/TC genotypes (OR 1.09, 95% CI 1.01-1.19, P 0.043). The association was more pronounced in non-drinkers in the recessive model (OR 1.13, 95% CI 1.01-1.27, P 0.029). A significantly increased risk of ESCC associated with miR-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. This study suggests that miR-196a2 rs11614913 and miR-499 rs3746444 are associated with an increased ESCC risk in a Chinese population.

Association Study of Single Nucleotide Polymorphisms inXRCC1Gene with Risk of Hepatocellular Carcinoma in Chinese Han Population

Hepatocellular carcinoma (HCC) is one of the most frequently causing cancer-related deaths worldwide. Previous evidence suggests that the X-ray repair cross-complementing group 1 gene (XRCC1) is an important candidate gene for influencing the risk of HCC. The aim of this study was to assess the association of XRCC1 genetic polymorphisms with the risk of HCC in Chinese Han population. A total of 1314 subjects, including 651 HCC patients and 663 healthy controls, were enrolled in this case-control study. Two genetic variants (c.1254C>T and c.1517G>C) in XRCC1 gene were genotyped by created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. Our data indicated that the allele and genotype frequencies of these two genetic variants were statistical difference in HCC cases and healthy controls. Association analyses suggested that these two genetic variants were statistically associated with the increased risk of HCC in all genetic models (for c.1254C>T, TT versus CC: OR = 2.30, 95% CI 1.61–3.28; CT versus CC: OR = 1.32, 95% CI 1.05–1.67; TT/CT versus CC: OR = 1.50, 95% CI 1.20–1.86; TT versus CT/CC: OR = 2.00, 95% CI 1.43–2.80; T versus C: OR = 1.47, 95% CI 1.25–1.73; for c.1517G>C, CC versus GG: OR = 1.90, 95% CI 1.34–2.69; GC versus GG: OR = 1.56, 95% CI 1.24–1.97; CC/GC versus GG: OR = 1.63, 95% CI 1.31–2.03; CC versus GC/GG: OR = 1.52, 95% CI 1.10–2.11; C versus G: OR = 1.45, 95% CI 1.23–1.70). The allele-T of c.1254C>T and allele-C of c.1517G>C genetic variants may contribute to HCC susceptibility in Chinese Han population.

Association of polymorphisms in survivin gene with the risk of hepatocellular carcinoma in Chinese han population: a case control study

BackgroundSurvivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of survivin gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of survivin gene polymorphisms with the risk of HCC in Chinese han population.MethodsA case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the survivin gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models.ResultsUsing univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (P > 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (OR = 0.46, 95% confidence interval (CI): 0.24~0.90, P = 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed.ConclusionsNo association between rs8073069, rs9904341 or rs1042489 in survivin gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC.