Association of LAMA1 Single-Nucleotide Polymorphisms with Risk of Esophageal Squamous Cell Carcinoma among the Eastern Chinese Population.

Introduction: LAMA1, also known as laminin subunit α1, is a member of the laminin family, which is widely reported to be a key basement membrane molecule that affects various biological activities and is associated with many kinds of diseases. We aimed to investigate the association between LAMA1single-nucleotide polymorphisms and the occurrence and progression of esophageal squamous cell carcinoma in the Chinese population. Method: 2,186 participants were collected retrospectively between October 2008 and January 2017, including 1,043 ESCC patients and 1,143 noncancer patients. A 2 mL blood sample was obtained intravenously for the LDR for SNP analysis. The 6 SNP loci of LAMA1 were selected and examined. We analyzed the association of several genetic models of 6 LAMA1 SNP loci, sex, age, smoking and drinking status, and the occurrence of esophageal squamous cell carcinoma. Results: In the rs62081531 G > A locus, genotype GA was a protective factor for ESCC compared with GG (OR: 0.830, P=0.046), especially among the younger and nondrinkers. At rs607230 T > C, genotype TC was linked with a lower risk of ESCC compared with TT. (OR: 0.613, P=0.034). Haplotype Frequencies revealed that Ars62081531Grs621993Ars539713Trs566655Ars73938538Crs607230 (OR: 0.803, P=0.028) and Grs62081531Grs621993Ars539713Trs566655Crs73938538Crs607230 (OR: 0.679, P=0.010) were strongly associated with lower susceptibility of ESCC. Conclusion: The LAMA1 rs62081531, rs539713, rs566655, and rs607230 polymorphisms were demonstrated to be related to susceptibility to ESCC in the Chinese population. LAMA1 SNPs may have a significant impact on the occurrence of esophageal cancer and may serve as potential diagnostic biomarkers.

A Connexin-Based Biomarker Model Applicable for Prognosis and Immune Landscape Assessment in Lung Adenocarcinoma.

Purpose: Gap junction protein (Connexin) family is the basic unit of cellular connection, whose multiple members were recently demonstrated to be associated with tumor progression. However, the expression pattern and prognostic value of connexin in lung adenocarcinoma (LUAD) have not yet been elucidated. Methods: Consensus cluster algorithm was first applied to determine a novel molecular subtype in LUAD based on connexin genes. The differentially expressed genes (DEGs) between two clusters were obtained to include in Cox regression analyses for the model construction. To examine the predictive capacity of the signature, survival curves and ROC plots were conducted. We implemented GSEA method to uncover the function effects enriched in the risk model. Moreover, the tumor immune microenvironment in LUAD was depicted by CIBERSORT and ssGSEA methods. Results: The integrated LUAD cohort (TCGA-LUAD and GSE68465) were clustered into two subtypes (C1 = 217 and C2 = 296) based on 21 connexins and the clinical outcomes of LUAD cases in the two clusters showed remarkable discrepancy. Next, we collected 222 DEGs among two subclusters to build a prognostic model using stepwise Cox analyses. Our proposed model consisted of six genes that accurately forecast patient outcomes and differentiate patient risk. GSEA indicated that high-risk group was involved in tumor relevant pathways were activated in high-risk group, such as PI3K/AKT signaling, TGF-ß pathway, and p53 pathway. Furthermore, LUAD cases with high-risk presented higher infiltration level of M2 macrophage and neutrophil, suggesting high-risk group were more likely to generate an immunosuppressive status. Conclusion: Our data identified a novel connexin-based subcluster in LUAD and further created a risk signature which plays a central part in prognosis assessment and clinical potency.

The Single Nucleotide Polymorphisms of AP1S1 are Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

Background: The σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population. Methods: A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step. Results: AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers. Conclusion: AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.

Case-control study on TP73 rs1801173 C > T gene polymorphism and susceptibility to gastric cancer in a Chinese Han population.

BACKGROUND: This study investigated the role of TP73 gene polymorphism, rs1801173on risk of gastric cancer. METHODS: We conducted a case-controlled study including 577 primary gastric cancer and 678 normal control cases. The target gene fragment was amplified using PCR using blood samples collected from patients. Allele analysis and genotyping were performed using snapshot method. RESULTS: The findings showed that the control group had consistent genotype frequency distribution and presented Hardy-Weinberg equilibrium. The results showed no significant differences in sex, drinking history and age distributions between subjects with the polymorphism and subjects in the control group. Smoking status was correlated with incidence of gastric cancer (P = 0.006). The rs1801173 locus of TP73 gene contained 3 genotypes including: TT, CT, and CT. Logistic regression analysis showed that distribution of recessive model and dominant model was comparable between the two groups before (P = 0.688; 0.937) or after (P = 0.703; 0.990) adjusting for confounders. The distribution frequency in case group was not significantly different relative to that of the control group (P = 0.763). CONCLUSION: Smoking can independently influence the risk of gastric cancer. TP73 gene rs1801173 polymorphism was not significantly correlated with risk of gastric cancer.

Research Progress of Circular RNA in Gastrointestinal Tumors.

circular RNA (circRNA) is a closed ring structure formed by cyclic covalent bonds connecting the 5'-end and 3'-end of pre-mRNA. circRNA is widely distributed in eukaryotic cells. Recent studies have shown that circRNA is involved in the pathogenesis and development of multiple types of diseases, including tumors. circRNA is specifically expressed in tissues. And the stability of circRNA is higher than that of linear RNA, which can play biological roles through sponge adsorption of miRNA, interaction with RNA binding protein, regulation of gene transcription, the mRNA and protein translation brake, and translation of protein and peptides. These characteristics render circRNAs as biomarkers and therapeutic targets of tumors. Gastrointestinal tumors are common malignancies worldwide, which seriously threaten human health. In this review, we summarize the generation and biological characteristics of circRNA, molecular regulation mechanism and related effects of circRNA in gastrointestinal tumors.

Case-Control Study on TNFRSF6B Gene Polymorphism and Susceptibility to Gastric Cancer in a Chinese Han Population.

PURPOSE: To explore the relationship between rs2297440 and rs2297441 polymorphisms of TNFRSF6B gene and susceptibility to gastric cancer. METHODS: A hospital-based case-control study was conducted. A total of 577 gastric cancer cases and 678 normal controls were recruited. Their genotypes were determined using the SnapShot method. RESULTS: The smoking rate in the case group (34.49%) was higher than that in the control group (27.29%). For TNFRSF6B rs2297440, among people <62 years old, the risk of gastric cancer in TC people was 1.84 times that in TT people. Among the non-drinking people, the risk of gastric cancer in the CC type was 0.66 times that in the TT+TC type. Among the drinking population, the risk of gastric cancer in the TC type was 1.67 times that in the TT type, and the risk in the TC+CC type was 1.70 times that in the TT type. As for TNFRSF6B rs2297441, in males and non-drinkers, the risk of gastric cancer in the AG type was less than that in the GG type. No matter how old the patient is, the risk of gastric cancer in the AA type was less than that in the AG+GG type. CONCLUSION: A correlation exists between smoking and gastric cancer. For TNFRSF6B rs2297440, the TC genotype may be a risk factor for gastric cancer in people <62 years old. In the non-drinking population, the homozygous mutant of CC may be a protective factor for gastric cancer. In the drinking population, TC type may be a risk factor, whereas the TC+CC type dominated by C may be a protective factor. For TNFRSF6B rs2297441, the AG genotype may be a risk factor for gastric cancer in males and non-drinkers. The AA homozygous mutant may be a protective factor for gastric cancer.

The Relationship Between Single Nucleotide Polymorphisms of SMAD3/SMAD6 and Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

BACKGROUND: The TGF-ß signal pathways play a key role in the development and promotion of squamous cell carcinoma (SCC). The pathway is mediated by the SMAD family proteins that include SMAD3 and SMAD6. Our study aimed to evaluate the relationship between single nucleotide polymorphism (SNP) of SMAD3/SMAD6 and susceptibility to esophageal squamous cell carcinoma (ESCC) in the Chinese population. PATIENTS AND METHODS: This was a hospital-based case-control study compromised of 1043 ESCC patients and 1315 non-cancer patients. Seven SMAD3/SMAD6 (rs8028147, rs3743343, rs3743342, rs8025774, rs8031440, rs803167, and rs34643453) SNPs were selected and used to evaluate their correlation with ESCC susceptibility. Genetic model tests, stratified analyses, linkage disequilibrium analyses, and haplotype analyses were performed in our study. RESULTS: Participants with SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A or rs8031627 G>A had a significantly higher risk of ESCC. This was more evident in males, older patients (>63 years), smokers, and non-alcohol drinking participants. Linkage disequilibrium analyses further revealed that there were strong correlations between SMAD3 rs3743342 C>T, rs8025774 C>T, rs8031440 G>A, and rs8031627 G>A. In the same line, haplotype analyses revealed that SMAD3 ACCCGGSMAD6A and SMAD3AGCCGGSMAD6A were associated with less susceptibility to ESCC while SMAD3ATTTAASMAD6A was associated with a higher risk of ESCC. CONCLUSION: SNPs of SMAD3 were related to higher susceptibility to ESCC. As such, they may contribute to the development of viable strategies for early diagnosis and treatment of ESCC. However, more detailed association mechanisms between SMAD3/SMAD6 SNPs and ESCC need further experiments to prove.

Association of Genetic Polymorphisms in FOXA1 with the Progression of Genetic Susceptibility to Gastric Cancer.

OBJECTIVE: To investigate the relationship between polymorphism of FOXA1 gene rs12894364 and rs7144658 and susceptibility to gastric cancer. METHODS: A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele was tested through a snapshot method. RESULTS: There was no significant difference in the frequency distribution of genotype between the case group and control group (P > 0.05). Stratified analyses showed the SNPs were not correlated with the susceptibility of GC according to different age, gender, cigarette smoking, and alcohol drinking status. CONCLUSION: There is no significant correlation between the polymorphisms of FOXA1 gene rs12894364 and rs7144658 and the risk of gastric cancer.

Association between apurinic/apyrimidinic endonuclease 1 rs1760944 T>G polymorphism and susceptibility of cancer: a meta-analysis involving 21764 subjects.

BACKGROUND: Previous case-control studies have suggested that apurinic/apyrimidinic endonuclease 1 (APE1) rs1760944 T>G polymorphism may be associated with cancer risk. Here, we carried out an updated meta-analysis to focus on the correlation between APE1 rs1760944 T>G locus and the risk of cancer. METHODS: We used the crude odds ratios (ORs) with their 95% confidence intervals (CIs) to evaluate the possible relationship between the APE1 rs1760944 T>G polymorphism and cancer risk. Heterogeneity, publication bias and sensitivity analysis were also harnessed to check the potential bias of the present study. RESULTS: Twenty-three independent studies involving 10166 cancer cases and 11598 controls were eligible for this pooled analysis. We found that APE1 rs1760944 T>G polymorphism decreased the risk of cancer in four genetic models (G vs. T: OR, 0.87; 95% CI, 0.83-0.92; P<0.001; GG vs. TT: OR, 0.77; 95% CI, 0.69-0.86; P<0.001; GG/TG vs. TT: OR, 0.83; 95% CI, 0.77-0.89, P<0.001 and GG vs. TT/TG: OR, 0.85; 95% CI, 0.80-0.92, P<0.001). Results of subgroup analyses also demonstrated that this single-nucleotide polymorphism (SNP) modified the risk among lung cancer, breast cancer, osteosarcoma, and Asians. Evidence of publication bias was found in the present study. When we treated the publication bias with 'trim-and-fill' method, the adjusted ORs and CIs were not significantly changed. CONCLUSION: In conclusion, current evidence highlights that the APE1 rs1760944 T>G polymorphism is a protective factor for cancer susceptibility. In the future, case-control studies with detailed risk factors are needed to confirm or refute our findings.

PADI4 rs2240337 G>A polymorphism is associated with susceptibility of esophageal squamous cell carcinoma in a Chinese population.

BACKGROUND: Esophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC. METHODS: We conducted a hospital based case-control study to evaluate the genetic susceptibility of SNPs on the development of EC. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. Seven PADI4 SNPs were determined by ligation detection reaction method. RESULTS: Our findings suggested that the PADI4 rs2240337 GA/AA variants were significantly associated with decreased risk of ESCC. Haplotype PADI4 Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562 polymorphism was correlated with decreased susceptibility to ESCC, while Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was correlated with increased susceptibility of ESCC. Stratification analyses demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366 AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype. Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT, rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years), rs11203366 AA genotype was associated with increased risk of ESCC. PADI4 rs1886302 CC variant was associated with ESCC susceptibility in female cohort. CONCLUSIONS: Our study suggested that PADI4 rs2240337 G>A polymorphism may be correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered susceptibility of ESCC based on sex, age, smoking status and alcohol consumption. However, larger studies among different ethnic populations and further experiments using genetically mutated cells or animals are warranted to verify our conclusion.

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.

Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 Chinese Han subjects.

In this study, we aimed to determine the potential association of MTHFR tagging single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric junction adenocarcinoma (EGJA). MTHFR rs1801133 G>A, rs3753584 T>C, rs4845882 G>A, rs4846048 A>G and rs9651118 T>C polymorphisms were genotyped in 1,677 healthy individuals and 1,063 patients with EGJA. We found that MTHFR rs1801133 G>A polymorphism was significantly associated with the risk of developing EGJA (AA vs. GG: adjusted P = 0.001; GA/AA vs. GG: adjusted P = 0.007 and AA vs. GA/GG: adjusted P = 0.001). However, for MTHFR rs4845882 G>A polymorphism, the decreased risk of EGJA was found in two genetic models (AA vs. GG: adjusted P = 0.002 and AA vs. GA/GG: adjusted P = 0.005). In addition, for MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms, a tendency to decreased risk of EGJA was noted. In a subgroup analysis, a significantly decreased risk of EGJA in <64 years subgroup was identified. We found that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Crs9651118, Grs1801133Crs3753584Ars4845882Ars4846048Trs9651118 and Grs1801133Trs3753584Ars4845882Grs4846048Trs9651118 haplotypes significantly decreased the risk of EGJA (P = 0.002, P < 0.001 and P = 0.038, respectively). In conclusion, our study demonstrates that MTHFR rs1801133 G>A may be associated with the increased risk of EGJA. Meanwhile, MTHFR rs3753584 T>C, rs4845882 G>A and rs9651118 T>C polymorphisms and haplotypes may decrease the risk of EGJA in Eastern Chinese Han population. Further studies with large sample size and detailed gene-environmental data are needed to validate our conclusion.

Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population.

OBJECTIVE: To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nucleotide polymorphisms (SNPs), including TP53BP1 rs560191 G>C, CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A, and six C1orf10/CRNN variants. We performed a hospital-based case-control study to evaluate the genetic effects of these SNPs. METHODS: Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscan(TM) Kit was used to determine their genotypes. RESULTS: When the TP53BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A or the six C1orf10/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. CONCLUSIONS: The results demonstrated that the functional polymorphism TP53BP1 rs560191 G>C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well-designed studies and further functional investigations are needed to confirm our 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.

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.