Increased Risk Of Esophageal Cancer Research Articles

Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.

In India, esophageal cancer (EC) is among the major cause of cancer-related deaths in both sexes. In recent past, autophagy has emerged as one of the crucial process associated with cancer. In the development of EC, the role of autophagy and the precise molecular mechanism involved has yet to be fully understood. Recently, a small number of studies have proposed how variations in autophagy genes affect the growth and development of EC. Micro-RNA's are also known to play a critical role in the development of EC. Here, we examined the relationship between the risk of EC and two single-nucleotide polymorphisms (SNPs) in the key autophagy genes, ATG10 rs1864183 and ATG16L1 rs2241880. We also analyzed the association of miR-107 and miR-126 with EC as these miRNA's are associated with autophagy. A total of 230 EC patients and 230 healthy controls from North-west Indian population were enrolled. ATG10 rs1864183 and ATG16L1 rs2241880 polymorphism were analyzed using TaqMan genotyping assay. Expression levels of miR-107 and miR-126 were analyzed through quantitative PCR using SYBR green chemistry. We found significant association of CT + CC genotype (OR 0.64, p = 0.022) in recessive model for ATG10 rs1864183 polymorphism with decreased EC risk. For ATG16L1 rs2241880 polymorphism significant association for AG genotype (OR 1.48, p = 0.05) and G allele (OR 1.43, p = 0.025) was observed for increased EC risk. Expression levels of miR-126 were also found to be significantly up regulated (p = 0.008). Our results suggest that ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 may be associated with esophageal carcinogenesis and warrant further investigation.

The Single Nucleotide Polymorphisms rs4143370 and rs34904192 in MIR155HG Were Associated with Esophageal Cancer Risk in the Chinese Han Population

Introduction: MIR155HG has been found to play an important role in malignant tumors, but little research has been done on its association with esophageal cancer (ESCC). The aim of this study was to investigate the relationship between MIR155HG polymorphisms and ESCC susceptibility in the Chinese Han population. Methods: 511 ESCC patients and 487 healthy controls were selected for this study. All subjects were genotyped using the Agena MassARRAY platform. We assessed the association between seven single nucleotide polymorphisms (SNPs) of the MIR155HG and ESCC risk by genetic model analysis. The false discovery rate (FDR) test and Bonferroni correction were usually used to detect false positives for the results. Meanwhile, the interaction between SNPs was analyzed by multifactor dimensionality reduction software to predict the ESCC risk. Results: The C allele of rs4143370 and the A allele of rs34904192 in MIR155HG can increase the risk of ESCC (odds ratio (OR) = 1.33, p = 0.024; OR = 1.30, p = 0.013). Furthermore, rs4143370 and rs34904192 were associated with an increased risk of ESCC. Stratified analysis showed that MIR155HG SNPs (rs4143370 and rs34904192) significantly increased ESCC risk in males. MIR155HG SNPs (rs4143370, rs34904192, and rs928883) were also strongly associated with an increased risk of ESCC in people aged >64 years. In addition, haplotype analysis of the seven SNPs of the MIR155HG showed that the CC haplotype was associated with ESCC risk (OR = 1.34, p = 0.024). Conclusion: This study revealed that MIR155HG SNPs were associated with an increased risk of ESCC. The results provided clues for clarifying the role of MIR155HG in ESCC.

S388 Risk of Esophageal Cancer in Achalasia: A Matched Cohort Study Utilizing the Veterans Affairs Achalasia Cohort (VA-AC)

Introduction: Achalasia is a postulated risk factor for esophageal cancer (EC) – both squamous cell carcinoma (SCC) and adenocarcinoma (AC). Evaluation of EC-associated risk factors and outcomes in achalasia are limited due to a lack of large, validated cohorts available for study. Our aim was to evaluate the risk of EC among individuals with compared to without achalasia utilizing a large, validated achalasia cohort: the Veterans Affairs Achalasia Cohort (VA-AC). Methods: We conducted a matched cohort study among US Veterans aged ≥18 years between 1999-2020. Individuals with achalasia from the VA-AC were matched to individuals without achalasia at a ratio of 1:4 on index achalasia encounter date, and by sex, year of birth, and first VA visit date +/- 180 days. Follow-up was censored at the outcome (EC), death from a non-EC related cause, or end of the study period. EC cases were ascertained from cancer registry and cause-specific mortality, with all cancer cases reviewed for verification. Descriptive statistics were performed for baseline characteristics. EC hazard functions were assessed using Cox regression models. Results: 1,866 Veterans with achalasia were matched to 7,464 Veterans without achalasia. Median age was 55 years (IQR 48-63), and 92% were male (Table). There were 17 EC cases among Veterans with achalasia (3 AC, 12 SCC, 2 unknown type) compared to 15 EC cases among Veterans without achalasia (11 AC, 1 SCC, 3 unknown). Median time from achalasia diagnosis to EC development was 3.0 years (IQR 1.3-9.1). Patients with achalasia had a 5.4-fold higher risk of EC (HR 5.4, 95% CI 2.8,10.5) compared to patients without achalasia. Higher cumulative incidence of EC (p< 0.0001, based on log-rank test; Figure) in those with vs without achalasia at 5-, 10- and 15-years follow-up was observed. In post hoc analysis, several individuals with EC also had candida esophagitis preceding their cancer diagnosis (12.5%) by median time 1.3 years (IQR 0.2-2.7). Based on univariate cox regression model, patients with vs without candida esophagitis had a 18.3-fold higher risk of EC (95% CI 6.2, 53.7). Conclusion: Using a national cohort of US Veterans, we found achalasia was associated with 5-fold increased EC risk compared to those without achalasia. Candida esophagitis exposure may also predict higher EC risk. Additional studies are needed to understand if this increased risk of EC warrants routine endoscopic surveillance in individuals with achalasia.Figure 1.: Cumulative Incidence of Esophageal Cancer Kaplan Meier curve demonstrating cumulative incidence at 5-, 10- and 15-year time points. Incidence at each time point was significantly higher for individuals with achalasia compared to individuals without achalasia. Table 1. - Achalasia ^ N = 1866 No AchalasiaN = 7464 Age, median (IQR) 55.0 (48.0 – 63.0) 55.0 (48.0 – 63.0) Males, n (%) 1725 (92.4) 6900 (92.4) Race/Ethnicity, n (%) Asian/Pacific Islander 23 (1.2) 113 (1.5) Black 378 (20.3) 1164 (15.6) Hispanic 125 (6.7) 326 (4.4) Multiracial/Other 25 (1.3) 157 (2.1) White 1208 (64.7) 4755 (63.7) Unknown 107 (10.1) 949 (12.7) BMI, median (IQR) 28.6 (25.1 – 32.9) 28.6 (25.4 – 32.6) Diabetes, n (%) 528 (28.3) 1686 (22.6) Smoking Status, n (%) Current 532 (28.5) 1592 (21.3) Former 386 (20.7) 1293 (17.3) Never 556 (29.8) 2398 (32.1) Unknown 392 (21.0) 2181 (29.2) Aspirin Exposure, n (%) 683 (36.6) 1699 (22.8) Barrett’s Esophagus, n (%) 125 (6.7) 189 (2.5) Candida Esophagitis, n (%) 64 (3.4) 7 (0.1) Esophageal Cancer, n (%) 17 (0.9) 15 (0.2) Squamous Cell Carcinoma 12 1 Adenocarcinoma 3 11 Unknown 2 3 *All variables are significant with p-value <.0001, except Age (Matched), Gender (Matched), and BMI which were not statistically significant at alpha=0.05.^Achalasia subjects were previously validated using an algorithm consisting of 3 or more ICD9 or ICD10 codes in a subject's lifetime plus a CPT code for esophageal manometry; the positive predictive value (PPV) for this algorithm to diagnose true achalasia subjects was 94% (95% confidence lower bound of 88.5%) BMI = body mass index; IQR = interquartile range.

Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies

ObjectiveMany laboratory studies have shown that tea consumption protected against the development of esophageal cancer (EC). However, in epidemiological studies, inconsistent or even contradictory results were frequently observed, especially when drinking tea at higher temperatures.MethodsWe conducted a meta-analysis based on published observational studies to explore whether hot tea consumption was a risk factor of EC. Relevant studies were searched in PubMed, Embase, and Web of science up to October 13, 2021, and we also manually retrieved the literature in the included studies and recent reviews.ResultsA total of 23 eligible reports were identified, including 5,050 cases and 10,609 controls, and a meta-analysis with Comprehensive Meta-Analysis (CMA) software (version 2.0) was conducted. A statistically significant increased EC risk was observed when drinking tea at higher temperature (odds ratios (ORs) = 1.79, 95% CI: 1.48–2.15, p = 0.00). Except for esophageal adenocarcinoma (EAC), this increased risk was also found in the majority of subgroups, which are the European and Australian populations.ConclusionsThis meta-analysis showed that people who drank hot tea had a significantly increased risk of Esophageal squamous cell carcinoma (ESCC), but no significant association for EAC.

PCR-RFLP genotyping analysis of TP53 Arg72Pro polymorphism and susceptibility to esophageal cancer in Pakistani population

Background and objectiveTumor suppressor gene TP53 is necessary for prevention of inappropriate cell proliferation and maintenance of genome integrity. TP53 Arg72Pro is the most studied single nucleotide polymorphism (SNP) associated with different cancers including esophageal cancer (EC). The study was established to investigate relationship between Arg72Pro polymorphism and EC susceptibility. Materials and methodsDNA from a total of 200 individuals (100 EC patients and 100 controls) were genotyped for TP53 codon 72 (Arg72Pro) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to estimate odds ratios and 95% confidence interval. ResultsSignificant differences in genotypes of Arg72Pro polymorphism between cases and controls were observed (P < 0.05). The patients represented 34% Pro/Pro, 44% Arg/Pro and 22% Arg/Arg whereas controls had 19% Pro/Pro, 42% Arg/Pro and 39% Arg/Arg genotypes. Pro/Pro variant showed 3.17-fold (95% CI: 1.47–6.83, P = 0.003) and Arg/Pro 1.71-fold (95% CI: 0.85–3.45, P = 0.071) increased EC risk compared with Arg/Arg. The Pro/Pro genotype was found to be significantly, whereas Arg/Pro was non-significantly associated with the esophageal cancer risk. Both males and females with Pro/Pro genotype were highly susceptible to cancer. Preserved meat consumers with Pro/Pro genotype were 4.8 fold (95% CI: 1.7–13.8) and subjects aged >50 with Pro/Pro were 4.6 fold (95% CI: 1.8–11.8) at increased risk of esophageal cancer. ConclusionsOur study suggests that Pro72 variant of TP53 polymorphism is highly correlated with increased EC. Further, the interaction between this polymorphism and tobacco consumption significantly affected EC development in Pakistani population.

The prevalence of esophageal cancer after caustic and pesticide ingestion: A nationwide cohort study.

Habits such as smoking and alcohol drinking and existing esophageal malfunction are considered the main risk factors for esophageal carcinogenesis. Caustic ingestion of acidic or alkaline agents or strong irritants can induce severe esophageal corrosive injury and increase esophageal cancer risk. We studied the relationship between esophageal carcinoma and acute detergent or pesticide poisoning by using nationwide health insurance data. Methodology/Principle findings: We compared a pesticide/detergent intoxication cohort (N = 21,840) and an age- and gender-matched control cohort (N = 21,840) identified from the National Health Insurance Research Database between 2000 and 2011. We used the multivariable Cox proportional model to determine esophageal carcinoma risk. The overall incidence density of esophageal cancer was 1.66 per 10,000 person-years in the comparison cohort and 4.36 per 10,000 person-years in the pesticide/detergent intoxication cohort. The corresponding adjusted hazard ratio (HR) for esophageal cancer was 2.33 (95% confidence interval [CI] = 1.41-3.86) in the pesticide/detergent intoxication cohort compared with the control cohort. Patients with corrosive and detergent intoxication did not have a higher risk of esophageal cancer (adjusted HR = 0.98, 95% CI = 0.29-3.33) than those without pesticide/detergent intoxication. However, patients with pesticide intoxication had a significantly higher risk of esophageal cancer (adjusted HR = 2.52, 95% CI = 1.52-4.18) than those without pesticide/detergent intoxication. Conclusion: In the present study, after adjusting for conventional risk factors, we observed that pesticide intoxication could exert substantial effects through increased esophageal cancer risk. However, patients with detergent intoxication may not have an increased risk of esophageal cancer.

Variants in multiple genes are associated with esophageal cancer risk in a Chinese Han population: A case-control study.

The present study investigated whether 16 single nucleotide polymorphisms (SNPs), selected based on minor allele frequencies, Hardy-Weinberg equilibrium and reported SNPs related to the susceptibility of certain gastrointestinal cancer, were associated with esophageal cancer (EC) risk in a Chinese Han population. We genotyped 16 SNPs among 506 cases and 507 controls using Agena MassARRAY (Agena, San Diego, CA, USA). The association between 16 SNPs and EC risk was analyzed by a chi-squared test and genetic model analysis. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). rs1050631 and the rs6214 were associated with a decreased EC risk (OR = 0.75, p = 0.038; OR = 0.74, p = 0.045, respectively). In stratification analysis, the rs9868873 was associated with an increased EC risk (age < 64 years) (OR = 5.03, p = 0.005). The rs6214 was associated with a decreased EC risk (age < 64 years) (OR = 0.59, p = 0.025). The rs861530 was significantly associated with a decreased EC risk (age ≥ 64 years) (OR = 0.67, p = 0.046). rs1050631 was associated with a decreased EC risk in males (OR = 0.71, p = 0.034). In the stratified analysis of clinical stage III/IV, the rs1800566 was associated with a decreased EC risk (OR = 0.49, p = 0.024). Finally, the rs1052133 was associated with an elevated EC risk in the stratified analysis of lymph node metastasis (OR = 1.73, p = 0.025). The findings of the present study demonstrate that SLC39A6, IGF1, SEMA5B, XRCC3, NQO1 and OGG1 polymorphisms were associated with EC risk under multiple models.

Genetic variants in GHR and PLCE1 genes are associated with susceptibility to esophageal cancer.

BackgroundEsophageal cancer (EC) is the leading cause of cancer‐related mortality worldwide. The underlying genetic risk factors remain unclear. The association between gene growth hormone receptor (GHR) and phospholipase C epsilon 1 (PLCE1) polymorphisms and the EC risk were identified in this study.MethodsA total of 506 EC cases and 507 controls were included in this research. Two SNPs (rs6898743 of GHR and rs2274223 of PLCE1) were selected and genotyped. The associations between gene polymorphisms and the EC risk were assessed by logistic regression analysis. The databases RegulomeDB, GTEx, and UALCAN were used for functional annotations.ResultsIn the allelic frequencies analysis, the rs6898743 of GHR was associated with decreased susceptibility of EC (OR = 0.83, 95% CI: 0.70–1.00, p = 0.049), while rs2274223 of PLCE1 was associated with increased 0.25‐fold EC risk (OR = 1.25, 95% CI: 1.02–1.53, p = 0.037). The “GC” genotype of rs6898743 was associated with a 0.24‐fold decreased risk of EC under co‐dominant model (OR = 0.76, 95% CI: 0.58–0.99, p = 0.046), and the “GA” genotype of rs2274223 was associated with increased EC risk under co‐dominant model (OR = 1.36, 95% CI: 1.04–1.77, p = 0.023). Using GTEx database, rs2274223 was found to be significant associated with increased PLCE1 expression (p = 4.1 × 10−7) in esophagus muscularis. The UALCAN database demonstrated that the GHR gene was under‐expressed in esophageal cancer tissues (p = 0.017).ConclusionThe gene GHR and PLCE1 polymorphisms are associated with EC in the general population and the results need to be verified in future.

Traditional and Commercial Alcohols as Risk Factors for Esophageal Cancer in Tanzania

PURPOSE Esophageal cancer (EC) is one of the most common cancers in East Africa; however, risk factors that underly the high incidence in this region are not well understood. We aimed to investigate the association between exposure to specific alcohol subtypes and EC in Tanzania. METHODS We performed a secondary analysis of data from a hospital-based, case-control study conducted at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Cases of EC were identified between 2014 and 2016. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for gender and age (± 10 years). Interviews were conducted using a survey with culturally relevant and context-specific questions on alcohol and smoking exposure. Conditional logistic regression analyses were applied to evaluate specific associations of potential exposures and EC. RESULTS A total of 473 EC cases and 473 controls were enrolled. Alcohol consumption was reported in 61% and 64% of cases and controls, respectively. Neither ‘current use of alcohol (any type)’, nor ‘ever use’ were associated with EC; however, local brew consumption was associated with increased EC risk (odds ratio [OR], 2.01; 95% CI, 1.53 to 2.66; P &lt; .01). Increased risk was observed with consumption of gongo (OR, 2.91), komoni (OR, 2.41), wanzuki (OR, 2.40), kindi (OR, 3.13), and kangara (OR, 2.86). Smoking increased EC risk; however, it did not significantly modify the association between EC and alcohol subtypes. CONCLUSION This is the first case-control study to report a detailed analysis of alcohol exposures as a potential risk factor for EC in Tanzania. Although combined measures of alcohol use were not found to be associated with EC, several types of locally brewed alcohols emerged as risk factors. Additional research is needed to investigate these findings and examine the carcinogenic role of ingredients and/or contaminants, as well as any interactions with other putative risk factors in this region.

IL1R2 Polymorphisms are Associated with Increased Risk of Esophageal Cancer.

Esophageal cancer (EC) is the sixth leading cause of cancer death worldwide, and the overall incidence is increasing. The aim of this study was to evaluate the association between single nucleotide polymorphisms in IL1R2 and EC risk in the Chinese population. Genotyping of six SNPs of IL1R2 was performed with the Agena MassARRAY platform from 384 EC and 499 controls. The association between polymorphisms and EC risk was assessed by performing genetics models and haplotype analyses. Overall analysis results showed that the allele C of rs11674595 (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.14-1.77, p = 0.002) and allele G of rs2072472 (allele: OR = 1.35, 95% CI: 1.08-1.69, p = 0.008) were associated with an increased EC risk. The rs11674595 and rs2072472 were found to be correlated with EC risk under the codominant, dominant, and additive models. Stratification analysis found that rs11674595 and rs2072472 were associated with increased EC risk in male and in age > 55 years old subgroup. In addition, Crs11674595Grs4851527 haplotype was significantly associated with 1.44-fold increased risk of EC (95% CI: 1.12-1.84, p = 0.004). Our results reveal the significant association between SNPs (rs11674595 and rs2072472) in the IL1R2 and EC risk in the Chinese Han population. The findings may provide meaningful reference for the prevention and treatment of EC.

Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 (CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 (CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1. The glutathione S-transferase mu 1 (GSTM1) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population-based cohort study.

Existing evidence remains inconclusive as to how the association between inactive ALDH2 and esophageal cancer (EC) depends on alcohol consumption. The study is based on the China Kadoorie Biobank cohort, with 10 years follow‐up of 0.5 million adults aged 30–79 years. ALDH2 activity was assessed by both self‐reported flushing response and Glu504Lys (rs671 G > A) polymorphism. Among both male and female participants who consumed alcohol less than weekly (n = 69,519; 211 EC cases), low active or inactive ALDH2 was not associated with increased EC risk [HRs (95% CIs): GA vs. GG 0.75 (0.54, 1.04); AA vs. GG 1.01 (0.46, 2.20)]. Among male weekly alcohol consumers, both flushing response [n = 59,380; 501 EC cases; HRs (95% CIs): “soon after drinking” vs. “no” flushing response 1.45 (1.05, 2.01)] and rs671 [n = 10,692; 94 EC cases; GA vs. GG 3.31 (1.94, 5.67)] were associated with EC risk. The increased EC risk associated with “soon” response or rs671 GA was apparent in men consuming alcohol ≥30g/d. Among male daily consumers, the HRs (95% CIs) for EC associated with 15g/d of alcohol were 1.28 (1.15, 1.44) for “soon” response [vs. other responses: 1.12 (1.09, 1.15); p interaction = 0.047; n = 36,401, 425 EC cases] and 1.41 (1.08, 1.82) for rs671 GA [vs. GG: 1.16 (1.06, 1.27); p interaction = 0.493; n = 6,607, 80 EC cases]. Self‐reported flushing response had low sensitivity (56.8%) and high specificity (88.4%) in identifying rs671 A allele among male weekly alcohol consumers. In conclusion, low‐activity ALDH2 was associated with increased EC risk among male heavy alcohol consumers. More accurate measurement of alcohol‐related EC risk allows better achievement of precision prevention.

GSTM1 and GSTT1 Gene Polymorphisms, Gene-Gene Interaction, and Esophageal Carcinoma Risk: Evidence from an Updated Meta-Analysis.

Published data regarding the association between GSTM1 and/or GSTT1 gene polymorphisms and esophageal cancer (EC) susceptibility remain inconclusive. To clarify these associations, a meta-analysis was conducted. We conducted a comprehensive search in PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) for all such manuscripts published as of May 1, 2017. The pooled odds ratio (ORs) with confidence intervals (95% CI) were estimated for each study to assess the strength of the association. A subgroup analysis, a sensitivity analysis, and a publication bias analysis were also performed. Data from 41 studies comprising 5291 EC cases and 8191 controls were available for analysis of the GSTM1 polymorphism, and data from 31 studies comprising 4330 EC cases and 6558 controls were available for analysis of the GSTT1 polymorphism. Analyses of the GSTM1 polymorphisms demonstrated that there was a significantly increased EC risk in GSTM1 null genotype carriers (OR = 1.319, 95% CI = 1.125-1.546, p for heterogeneity <0.001). In subgroup analyses by ethnicity, and categories of EC, a significantly increased EC risk was found in Asians (OR = 1.457, 95% CI = 1.212-1.751, p for heterogeneity <0.001) and patients whose histological type was unknown. Analyses of the GSTT1 polymorphisms indicated a positive correlation between the GSTT1 null genotype and the EC risk (OR = 1.233, 95% CI = 1.044-1.455, p for heterogeneity <0.001). In subgroup analyses stratified by ethnicity and categories of EC, similar statistical associations were observed in Asians, esophageal squamous cell carcinoma (ESCC) patients, and ESCC on Asian population. In the GSTM1-GSTT1 interaction analysis, we discovered remarkably enhanced EC risk for patients with the GSTM1 and GSTT1 dual null genotypes (OR = 1.962, 95% CI = 1.178-3.268, p for heterogeneity <0.001) compared with the reference GSTM1 and GSTT1 dual positive genotype. We conclude that the GSTM1 and GSTT1 null genotypes are associated with increased genetic susceptibility to EC in the overall human population, particularly among Asians. In addition, our findings suggest that persons with a null genotype for both the GSTM1 and GSTT1 genes are at higher risk of developing EC. Further well-designed studies are needed to confirm these associations.

Association Studies of CYP1A1 Exon7 Polymorphism and -GSTM1 Interaction with Esophageal Cancer Risk: a Meta-Analysis in the Chinese Population.

Although many epidemiological studies have investigated the CYP1A1 exon7 polymorphism and -GSTM1 interaction with esophageal cancer (EC), definite conclusions cannot be drawn. This study was conducted to explore this association in the Chinese population using meta-analysis. Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine databases published through August 2015. The association of CYP1A1 exon7 polymorphisms and EC risk was estimated by odds ratio (ORs) with 95% confidence intervals (CIs). In addition, the interaction between the CYP1A1 exon7 and GSTM1 genotypes was assessed. A total of 13 case-control studies including 1781 EC cases and 1996 controls were included in this metaanalysis. Overall, significantly increased EC risk was associated with the CYP1A1 exon7 polymorphism (G vs. A OR = 1.36, 95% CI = 1.14 - 1.64; GG vs. AA: OR = 1.85, 95% CI = 1.22 - 2.79; GG vs. AG: OR = 1.41, 95% CI = 1.01 - 1.96; GG + AG vs. AA: OR = 1.47, 95% CI = 1.28 - 1.68; GG vs. AA + AG: OR = 1.60, 95% CI = 1.10 - 2.31). In a subgroup analyses stratified by geographic areas, histopathology type and source of controls, the significant risk was found in hospital-based population, in South and North China. Analysis of CYP1A1- GSTM1 interaction did find synergistic interaction between these two genes. This meta-analysis provides the evidence that CYP1A1 exon7 polymorphism may contribute to the EC development in the Chinese population, and CYP1A1- GSTM1 interaction might elevate the risk.

Meta-analysis demonstrates association of XRCC1 genetic polymorphism Arg399Gln with esophageal cancer risk in the Chinese population

We made a meta-analysis of the association between X-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and esophageal cancer (EC) risk. Statistical analysis was performed with the Review Manager version 4.2.8 software program and STATA version 11.0. We selected 16 case-control studies for this meta-analysis, including 3591 EC cases and 5752 controls. Overall, the Gln399 allele was not associated with EC risk, compared with the Arg399 allele in the populations included in the analysis. However, stratified analysis revealed that the Gln399 allele was associated with increased EC risk among the Chinese population in a recessive model [odds ratio (OR) = 1.42; 95% confidence interval (95%CI) = 1.07-1.90; P = 0.02 for heterogeneity] and by homozygote contrast (OR = 1.43; 95%CI = 1.05-1.96; P = 0.02 for heterogeneity), particularly for the tumor histology of squamous cell carcinoma (OR = 1.46; 95%CI = 1.10-1.95 for the recessive model and OR = 1.42; 95%CI = 1.03-1.95 for the homozygote contrast). We conclude that the XRCC1 Arg399Gln polymorphism has potential as a biomarker for EC susceptibility in the Chinese population, particularly for squamous cell carcinoma.

Dietary patterns and the risk of esophageal cancer

The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.

Study on the association of cytochrome P450 polymorphisms and the risk of esophageal cancer: a meta-analysis

To examine the association between CYP1A1 polymorphisms (MspI and Ile/Val) and esophageal cancer (EC) by systematically reviewing the risk of the original studies. Data from 16 papers (8 for MspI, 14 for Ile/Val) regarding case-control studies on the association of cytochrome P450 polymorphisms and risk of esophageal cancer was analyzed by dominant model (variant genotype vs. wild-type genotype) through meta-analysis. Stratified analysis was carried out according to the pathological types. In systematical analysis, CYP1A1 MspI variant genotype (TC + CC) had no association with EC risk (OR = 1.17, 95%CI: 0.82 - 1.66). Similar results were observed in esophageal squamous-cell carcinoma (ESCC) (OR = 1.17, 95%CI: 0.82 - 1.69) and esophageal adenocarcinoma (EAC) (OR = 1.39, 95%CI: 0.67 - 2.09). Individuals with the CYP1A1 Ile/Val variant genotype (Ile/Val + Val/Val) had an increased risk for EC, when comparing with wild type (Ile/Ile), with an OR of 1.39 (95%CI: 1.07 - 1.80). CYP1A1 Ile/Val variant genotype could increase the risk of ESCC (OR = 1.43, 95%CI: 1.07 - 1.91) but no significant association was found with EAC (OR = 1.20, 95%CI: 0.62 - 2.30). CYP1A1 gene polymorphism Ile/Val might have played a role in the development of ESCC but CYP1A1 MspI polymorphism might not be associated with the susceptibility of EC.

Two Functional Coding Single Nucleotide Polymorphisms in STK15 (Aurora-A) Coordinately Increase Esophageal Cancer Risk

STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation and cytokinesis, and is considered to be a cancer susceptibility gene in mice and humans. Two coding single nucleotide polymorphisms in Aurora-A, 91T>A [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A. We evaluated the association between these coding single nucleotide polymorphisms and esophageal cancer risk by genotyping 197 esophageal cancer cases and 146 controls. Haplotype 91A-169A (I31/I57) was observed to be statistically more frequent in cancer cases (odds ratio, 3.1452; 95% confidence interval, 1.0258-9.6435). Functional differences among the four isoforms were then analyzed to reveal the source of the cancer risk. Kinase activity levels of I31/I57 and F31/I57 were reduced to 15% and 40% compared with I31/V57 in vivo and in vitro. We considered the differences between the kinase activities and divided individuals into four categories of Aurora-A haplotype combination. Category I had 57.5% or less kinase activity compared with the most common category, category III, and had a significantly higher estimated cancer risk (odds ratio, 5.5328; 95% confidence interval, 1.8149-16.8671). Abnormal nuclear morphology, a characteristic of genomic instability, was observed to be 30 to 40 times more frequent in human immortalized fibroblast cells overexpressing I31/I57 or F31/I57 compared with the others. Furthermore, significantly higher levels of chromosomal instability were observed in cancers in category I (homozygote 91T-169A) than those in category III (homozygous 91A-169G). These results indicate that the less kinase active Aurora-A haplotype combinations might induce genomic instability and increase esophageal cancer risk either in a recessive or a dominant manner.

Research News

University of Melbourne Offers Hope for Diabetic Blindness. Gene Silencing Technology Unveiled. Multiple Sclerosis and Rheumatoid Arthritis Drug Ready for Human Testing. Vaccinating against CMV. Chinese Fish Sauce May Increase Esophageal Cancer Risk. India to Help in Safer Rotavirus Vaccine. Bio-fertiliser Bacteria Developed. Biodegradable Plastic for Computer Housing. Researchers Find Neural Mechanisms of Motivation and Reward. Scientist Hopes to Recreate LUCA Gene. Probiotics Study in Combating Eczema. Sensitive DNA Technique for Solving Old Crime Cases. Study on Link between Cot-death and Teen Fatalities. Singapore Researcher Ups IVF Success Rate. Robotic System Investigated for Laparoscopic Cholecystectomy. Method against Diabetes-related Blindness Ready for Human Trial.