Keratin 17 and Collagen type 1 genes: Esophageal cancer molecular marker discovery and evaluation.

One hundred eighty pairs of tissues of esophageal squamous cell carcinoma (ESCC) were tested by the transcriptome sequencing in order to explore etiology factors. The chi-square test and correlation analysis demonstrated that the relative expression levels of keratin 17 (KRT17) and collagen type I α1 chain (COL1A1) were significantly higher in EC with diabetes. Expression of KRT17 was correlated with blood glucose (r = 0.204, p = 0.001) and tumor size (r = -0.177, p = 0.038) in patients. COL1A1 correlated with age (r = -0.170, p = 0.029) and blood glucose levels (r = 0.190, p = 0.015). Experimental results of qRT-PCR: KRT17 and COL1A1 genes were highly expressed in ESCC (p < 0.05). When the two genes were used as a combination test, the positive detection rate of EC was 90.6%, and the ROC curve had greater power. The KRT17 and COL1A1 genes had the potential to be biomarkers for the diagnosis of ESCC.

Identification and Validation of Common Reference Genes for Normalization of Esophageal Squamous Cell Carcinoma Gene Expression Profiles.

Esophageal squamous cell carcinoma (ESCC) is one of the subtypes of esophageal cancer with Chinese characteristics, and its five-year survival rate is less than 20%. Early diagnosis is beneficial to improving the survival rate of ESCC significantly. Quantitative Real-Time Polymerase Chain Reaction is a high-throughput technique that can quantify tumor-related genes for early diagnosis. Its accuracy largely depends on the stability of the reference gene. There is no systematic scientific basis to demonstrate which reference gene expression is stable in ESCC and no consensus on the selection of internal reference. Therefore, this research used four software programs (The comparative delta-Ct method, GeNorm, NormFinder, and BestKeeper) to evaluate the expression stability of eight candidate reference genes commonly used in other tumor tissues and generated a comprehensive analysis by RefFinder. Randomly selected transcriptome sequencing analysis confirmed the SPP1 gene is closely related to ESCC. It was found that the expression trend of SPP1 obtained by RPS18 and PPIA as internal reference genes were the same as that of sequencing. The results show that RPS18 and PPIA are stable reference genes, and PPIA + RPS18 are a suitable reference gene combination. This is a reference gene report that combines transcriptome sequencing analysis and only focuses on ESCC, which makes the quantification more precise, systematic, and standardized, and promotes gene regulation research and the early diagnosis of ESCC in the future.

Prognostic value of lncRNAs related to fatty acid metabolism in lung adenocarcinoma and their correlation with tumor microenvironment based on bioinformatics analysis.

Background: As a key regulator of metabolic pathways, long non-coding RNA (lncRNA) has received much attention for its relationship with reprogrammed fatty acid metabolism (FAM). This study aimed to investigate the role of the FAM-related lncRNAs in the prognostic management of patients with lung adenocarcinoma (LUAD) using bioinformatics analysis techniques. Methods: We obtained LUAD-related transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) database. The lncRNA risk models associated with FMA were constructed by single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network (WGCNA), differential expression analysis, overlap analysis, and Cox regression analysis. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were utilized to assess the predictive validity of the risk model. Gene set variation analysis (GSVA) revealed molecular mechanisms associated with the risk model. ssGSEA and microenvironment cell populations-counter (MCP-counter) demonstrated the immune landscape of LUAD patients. The relationships between lncRNAs, miRNAs, and mRNAs were predicted by using LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using DAVID v6.8. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic lncRNAs. Results: We identified 249 differentially expressed FMA-related lncRNAs in TCGA-LUAD, six of which were used to construct a risk model with appreciable predictive power. GSVA results suggested that the risk model may be involved in regulating fatty acid synthesis/metabolism, gene repair, and immune/inflammatory responses in the LUAD process. Immune landscape analysis demonstrated a lower abundance of immune cells in the high-risk group of patients associated with poor prognosis. Moreover, we predicted 279 competing endogenous RNA (ceRNA) mechanisms for 6 prognostic lncRNAs with 39 miRNAs and 201 mRNAs. Functional enrichment analysis indicated that the ceRNA network may be involved in the process of LUAD by participating in genomic transcription, influencing the cell cycle, and regulating tissue and organogenesis. In vitro experiments showed that prognostic lncRNA CTA-384D8.35, lncRNA RP5-1059L7.1, and lncRNA Z83851.4 were significantly upregulated in LUAD primary tumor tissues, while lncRNA RP11-401P9.4, lncRNA CTA-384D8.35, and lncRNA RP11-259K15.2 were expressed at higher levels in paraneoplastic tissues. Conclusion: In summary, the prognostic factors identified in this study can be used as potential biomarkers for clinical applications. ceRNA network construction provides a new vision for the study of LUAD pathogenesis.

Metabolomics of Esophageal Squamous Cell Carcinoma Tissues: Potential Biomarkers for Diagnosis and Promising Targets for Therapy.

Background: The incidence of esophageal squamous cell carcinoma in China ranks first in the world. The early diagnosis technology is underdeveloped, and the prognosis is poor, which seriously threatens the quality of life of the Chinese people. Epidemiological findings are related to factors such as diet, living habits, and age. The specific mechanism is not clear yet. Metabolomics is a kind of omics that simultaneously and quantitatively analyzes the comprehensive profile of metabolites in living systems. It has unique advantages in the study of the diagnosis and pathogenesis of tumor-related diseases, especially in the search for biomarkers. Therefore, it is desirable to perform metabolic profiling analysis of cancer tissues through metabolomics to find potential biomarkers for the diagnosis and treatment of esophageal squamous cell carcinoma. Methods: HPLC-TOF-MS/MS technology and Illumina Hiseq Xten Sequencing was used for the analysis of 210 pairs of matched esophageal squamous cell carcinoma tissues and normal tissues in Zhenjiang City, Jiangsu Province, a high-incidence area of esophageal cancer in China. Bioinformatics analysis was also performed. Results: Through metabolomic and transcriptomic analysis, this study found that a total of 269 differential metabolites were obtained in esophageal squamous cell carcinoma and normal tissues, and 48 differential metabolic pathways were obtained through KEGG enrichment analysis. After further screening and identification, 12 metabolites with potential biomarkers to differentiate esophageal squamous cell carcinoma from normal tissues were obtained. Conclusions: From the metabolomic data, 4 unknown compounds were found to be abnormally expressed in esophageal squamous cell carcinoma for the first time, such as 9,10-epoxy-12,15-octadecadienoate; 3 metabolites were found in multiple abnormal expression in another tumor, but upregulation or downregulation was found for the first time in esophageal cancer, such as oleoyl glycine; at the same time, it was further confirmed that five metabolites were abnormally expressed in esophageal squamous cell carcinoma, which was similar to the results of other studies, such as PE.

Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma.

Background: The most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD. Methods: This particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program. Results: We detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs). Conclusion: In conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.

Polymorphisms of VDR gene and risk of gastric cardiac adenocarcinoma in Chinese population.

Vitamin D receptor (VDR) gene polymorphisms have been reported to increase susceptibility to some malignant tumors, yet the effect on gastric cardiac adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital-based case-control study to examine the correlation of single nucleotide polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608 controls were enrolled in the study. Using ligation detection reaction, we found that the variant alleles of the four polymorphisms were not associated with risk of gastric cardiac adenocarcinoma. Further stratified analyses showed that there was an increased risk associated with VDR rs1989969 polymorphism among patients who were drinking or aged <60. The haplotypes VDR Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis of gastric cardiac adenocarcinoma, especially increased the risk in the younger and alcohol drinking Chinese population.

Association of ALDH3B2 gene polymorphism and risk factors with susceptibility of esophageal squamous cell carcinoma in a Chinese population: a case-control study involving 2,358 subjects.

BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide. The interaction of environmental risk factors and genetic factors might contribute to the carcinogenesis of EC synergistically. RESULTS: All seven single locus polymorphisms of ALDH3B2 were not associated with risk of ESCC as evaluated by allelic, dominant, co-dominant, recessive and Cochran-Armitage trend tests. Stratified analyses showed these SNPs were not correlated with the susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. None of the major haplotypes were related with ESCC susceptibility. MATERIALS AND METHODS: We conducted a hospital-based case-control study to evaluate the combined effects of environmental risk factors and the single nucleotide polymorphisms (SNPs) of ALDH3B2 gene on the development of esophageal squamous carcinoma (ESCC). A total of 1043 ESCC cases and 1315 controls were recruited for this study. Seven ALDH3B2 SNPs and four environmental factors were selected as independent variables. ALDH3B2 SNPs were determined by ligation detection reaction method. CONCLUSIONS: Our study suggested that ALDH3B2 rs34589365, rs3741172, rs4646823, rs78402723, rs7947978, rs866907 and rs9787887 polymorphisms were not implicated with altered susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. Yet this conclusion needs to be verified in larger studies among different ethnic populations with validation design, the biological function of these SNPs in carcinogenesis are subject to further investigation.

RANK rs1805034 T>C Polymorphism Is Associated with Susceptibility to Gastric Cardia Adenocarcinoma in a Chinese Population.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is a common malignant tumor of the digestive tract with a high incidence in China. Genetic factors such as single nucleotide polymorphisms (SNPs) may contribute to the carcinogenesis of GCA. METHODS: We conducted a hospital-based case-control study to evaluate the genetic association of functional SNPs with susceptibility to GCA development. A total of 330 GCA cases and 608 controls were recruited for this study. The SNPs OPG rs3102735 T>C and rs2073618 G>C, RANK rs1805034 T>C, and RANKL rs9533156 T>C and rs2277438 A>G were determined using the ligation detection reaction method. RESULTS: Our findings suggest that RANK rs1805034 T>C is associated with susceptibility to GCA, which is more evident among male patients, elderly patients (≥ 60 years), smokers, and patients who do not consume alcohol. CONCLUSION: Based on our findings, the functional SNP RANK rs1805034 T>C may be an indicator for individual susceptibility to GCA. However, further larger studies with other ethnic populations and tissue-specific biological characterization are required to confirm the current findings.

Long noncoding RNAs POLR2E rs3787016 C/T and HULC rs7763881 A/C polymorphisms are associated with decreased risk of esophageal cancer.

Worldwide, rates of esophageal cancer have been keeping highly in recent decades. Genetic variants in multiple cellular pathways might play an important role in altering risk of esophageal carcinoma. In this study, long noncoding RNAs (lncRNAs) functional single nucleotide polymorphisms (SNPs) were investigated in Chinese Han populations. We have genotyped the ANRIL rs2151280 T/C, POLR2E rs3787016 C/T, and HULC rs7763881 A/C SNPs in 380 esophageal squamous cell carcinoma (ESCC) cases and 380 cancer-free controls. POLR2E rs3787016 C/T was associated with a significantly decreased risk for ESCC (CT vs. CC: OR 0.62, 95 % CI 0.44-0.87, P = 0.005; adjusted OR 0.62, 95 % CI 0.44-0.87, P = 0.005). The other SNP, HULC rs7763881, also showed a suggestive association (AC vs. AA: OR 0.70, 95 % CI 0.50-0.98, P = 0.037; adjusted OR 0.69, 95 % CI 0.49-0.97, P = 0.031). ANRIL rs2151280 T/C SNP was not associated with risk of ESCC. In the future, larger studies with other ethnic populations, tissue-specific biological characterization, and detailed individual information should be undertaken to validate current findings.

Methyl-CpG binding domain 4 tagging polymorphisms and esophageal cancer risk in a Chinese population.

In 2009, esophageal cancer was recorded as the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Genetic factors might play an important role in the carcinogenesis of ESCC. We conducted a hospital-based case-control study to evaluate the association between methyl-CpG binding domain 4 (MBD4) rs3138373 A>G, rs2005618 T>C, and rs3138355 G>A tag single nucleotide polymorphisms and the risk of developing ESCC. A total of 629 ESCC patients and 686 controls were recruited. Genotypes were determined using the ligation detection reaction method. When the MBD4 rs3138355 GG homozygous genotype was used as the reference group, the GA, AA, and GA/AA genotypes were not associated with ESCC risk. In the recessive model, when the MBD4 rs3138355 GG/GA genotypes were used as the reference group, the AA homozygous genotype was associated with a 28% decreased risk for ESCC (AA vs. GG/GA: adjusted odds ratio=0.72, 95% confidence interval=0.53-0.99, P=0.040). The MBD4 rs3138373 A>G and rs2005618 T>C single nucleotide polymorphisms were not associated with ESCC risk. The MBD4 rs3138355 G>A polymorphism was associated with a significantly decreased risk of ESCC among male and older patients. The MBD4 rs3138355 GG genotype was associated with a decreased risk of ESCC among male patients and the elderly. Additional, larger studies are required to confirm these current findings.

p21, p53, TP53BP1 and p73 polymorphisms and the risk of gastric cardia adenocarcinoma in a Chinese population.

Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors and among the leading causes of cancer-related death. Genetic factors might play an important role in GCA carcinogenesis. Here, we performed a hospital-based case-control study to evaluate the effect of functional p21, p53, TP53BP1 and p73 single nucleotide polymorphisms (SNPs) on the risk of GCA. The study included 330 GCA cases and 608 controls. Genotypes were determined using the ligation detection reaction (LDR) method. The p21 rs1059234 TT, p21 rs3176352 GC/CC, p21 rs762623 GA and TP53BP1 rs560191 CC genotypes were associated with the risk of GCA, and a genotype combination effect was observed. After Bonferroni correction, the association remained significant for TP53BP1 rs560191 G > C, whereas the remaining four SNPs showed no association between the polymorphisms and GCA risk in all comparison models. Further large replication studies are needed to confirm the present findings.

Uracil-DNA glycosylase (UNG) rs246079 G/A polymorphism is associated with decreased risk of esophageal cancer in a Chinese population.

Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. In addition to environmental risk factors, genetic factors might play an important role in esophageal cancer carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between functional single nucleotide polymorphisms (SNPs) in uracil-DNA glycosylase (UNG) and the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The UNG rs3219218 A/G and UNG rs246079 G/A genotypes were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the UNG rs246079 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk for ESCC (GA vs. GG: adjusted OR 0.67, 95 % CI 0.49-0.91, P = 0.011); the AA genotype was not associated with the risk of ESCC. In stratification analyses, a significantly decreased risk of ESCC associated with the UNG rs246079 G/A polymorphism was evident among women, younger patients and never-smokers and never-drinkers. The UNG rs3219218 A/G polymorphism was not associated with the risk for ESCC. These findings indicated that UNG rs246079 G/A might contribute to a decreased risk of ESCC in specific populations. Because of the limited sample size, further studies including a larger and more diverse population, as well as tissue-specific biological characterization, are required to confirm the current findings.

RANK rs1805034 T>C polymorphism is associated with susceptibility of esophageal cancer in a Chinese population.

Esophageal cancer remains the sixth leading cause of cancer associated death and eighth most common cancer worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of esophageal cancer. Here, we conducted a hospital based case-control study to evaluate the genetic susceptibility of functional SNPs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. The OPG rs3102735 T>C, rs2073618 G>C, RANK rs1805034 T>C, RANKL rs9533156 T>C and rs2277438 A>G were determined by ligation detection reaction method. Our findings suggested that RANK rs1805034 T>C is associated with the susceptibility of ESCC, which is more evident in male and elder (≥63) patients. Our study provides the first evidence that functional polymorphisms RANK rs1805034 T>C may be an indicator for individual susceptibility to ESCC. However, further larger studies among different ethnic populations are warranted to verify our conclusion.

TERT-CLPTM1L Rs401681 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

BACKGROUND: Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis. METHODS: We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method. RESULTS: When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.58-0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR  = 0.74, 95% CI  = 0.59-0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed. CONCLUSION: TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.

p21 rs3176352 G>C and p73 rs1801173 C>T polymorphisms are associated with an increased risk of esophageal cancer in a Chinese population.

OBJECTIVE: Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in esophageal squamous cell carcinoma (ESCC) carcinogenesis. DESIGNS AND METHODS: To evaluate the effect p21, p53, TP53BP1 and p73 single nucleotide polymorphisms (SNPs) on the risk of ESCC, we conducted a hospital based case-control study. A total of 629 ESCC cases and 686 controls were recruited. Their genotypes were determined using ligation detection reaction (LDR) method. RESULTS: When the p21 rs3176352 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of ESCC. When the p73 rs1801173 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly increased risk of ESCC. After Bonferroni correction, for p21 rs3176352 G>C, the pcorrect was still significant. For the other six SNPs, in all comparison models, no association between the polymorphisms and ESCC risk was observed. CONCLUSIONS: p21 rs3176352 G>C and p73 rs1801173 C>T SNPs are associated with increased risk of ESCC. To confirm the current findings, additional, larger studies and tissue-specific biological characterization are required.

N-acetyltransferase 2 polymorphisms and risk of esophageal cancer in a Chinese population.

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in the carcinogenesis of esophageal squamous cell carcinoma (ESCC). We conducted a hospital-based case-control study to evaluate ten NAT2 tagging single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction method. In the single locus analyses, there was a borderline statistically significant difference in genotype frequencies of NAT2 rs1565684 T>C SNP between the cases and the controls (p = 0.057). The NAT2 rs1565684 CC genotype was associated with a borderline significantly increased risk for ESCC (CC vs. TT: adjusted OR = 1.77, 95% CI = 0.97-3.21, p = 0.063 and CC vs. TT/TC: adjusted OR = 1.68, 95% CI = 0.93-3.04, p = 0.085). The association was evident among older patients and patients who never drunk. After the Bonferroni correction, in all comparison models, NAT2 rs1565684 T>C SNP was not associated with ESCC risk (p>0.05). For the other nine NAT2 SNPs, after Bonferroni correction, in all comparison models, the nine SNPs were also not associated with ESCC risk (p>0.05). Thus, nine NAT2 tagging SNPs were not associated with risk of ESCC. NAT2 rs1565684 T>C SNP might play a slight role in ESCC etiology. Additional, larger studies and tissue-specific biological characterization are required to confirm the current findings.

IL-15 receptor alpha rs2228059 A>C polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Esophageal cancer is very aggressive; genetic polymorphisms may explain in part the individual differences in esophageal cancer susceptibility. We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin (IL)-15 and IL-15 receptor alpha (IL-15RA) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan(TM) kit. The IL-15RA rs2228059 A>C polymorphism was associated with a decreased risk of ESCC in a recessive genetic model; However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated a significantly decreased risk of ESCC associated with the IL-15RA rs2228059 A>C polymorphism was evident among male, older, non-smoker, and non-drinker patients. These findings indicated that the functional polymorphism, IL-15RA rs2228059 A>C, might contribute to ESCC susceptibility. However, the statistical power of our study was limited because of the moderate sample size and absence of a validation cohort. Large well-designed studies are warranted to confirm our findings.

Caspase8 rs1035142 G>T polymorphism was associated with an increased risk of esophageal cancer in a Chinese population.

Esophageal cancer is one of the ten most common cancers in the world and has poor prognosis. Apoptosis is considered a fundamental component in cancer pathogenesis. We conducted a hospital-based case-control study to evaluate the genetic effects of 16 apoptosis associated single nucleotide polymorphisms (SNPs) on esophageal cancer development. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. Genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit. The caspase8 (CASP8) rs1035142 G>T polymorphism was associated with increased risk of ESCC by heterozygote comparison, homozygote comparison, a dominant genetic model and a recessive genetic model. However, no significant association was detected between the other 15 SNPs and ESCC risk. Stratified analyses indicated a significantly increased risk of ESCC associated with CASP8 rs1035142 G>T polymorphism was evident among all subgroups. These findings indicated that the functional polymorphism CASP8 rs1035142 G>T might contribute to ESCC susceptibility.

Vitamin D receptor gene polymorphisms and esophageal cancer risk in a Chinese population: a negative study.

Vitamin D receptor (VDR) gene polymorphisms have been reported to influence susceptibility to some malignant cancers. However, there were few published findings on the association between VDR polymorphisms and esophageal cancer susceptibility. Our investigation was aimed to obtain a precise estimation of the association between VDR polymorphisms and esophageal cancer susceptibility. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single-nucleotide polymorphisms VDR rs2107301 T>C, rs2228570 C>T, rs1989969 C>T and rs11568820 G>A on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. The genotypes were determined using ligation detection reaction method. There were no significant associations between the four VDR variants and ESCC risk. Stratified analyses indicated a significantly increased risk of ESCC associated with VDR rs2107301 T>C polymorphism among patients who were drinking. These findings demonstrated that the risk of ESCC associated with VDR rs2107301 T>C polymorphism may be modified by lifestyle factors such as drinking. However, the results should be validated in larger well-designed studies in future.

NQO1 rs1800566 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

BACKGROUND. Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Genetic factors may play an important role in the carcinogenesis of ESCC. METHODS. We conducted a hospital-based case-control study to evaluate functional NAD(P)H: quinone oxidoreductase 1 (NQO1) rs1800566 C>T and NQO2 rs2070999 G>A single-nucleotide polymorphisms on the risk of ESCC. A total of 629 patients with ESCC and 686 controls were recruited for this study. The genotypes were determined using the ligation detection reaction method. RESULTS. When the NQO1 rs1800566 CC homozygote genotype was used as the reference group, the TT genotype was associated with a significantly decreased risk of ESCC. In the recessive model, when the NQO1 rs1800566 CC/CT genotypes were used as the reference group, the TT homozygote genotype was associated with a 31% decreased risk of ESCC. A significantly decreased risk of ESCC was evident in patients with the NQO1 rs1800566 C>T polymorphism among females, those of a younger age (<63 years), those who had never smoked, those who consumed alcohol and those who did not. There was no association found between the NQO2 rs2070999 G>A polymorphism and ESCC risk. CONCLUSION. The NQO1 rs1800566 TT genotype was associated with a decreased risk of ESCC in a Chinese population. The association was evident among female patients, younger patients, patients who had never smoked, patients who consumed alcohol and those who did not. These findings need to be confirmed by repeating the study in a larger cohort of patients.