Esophageal Precancerous Lesions Research Articles

Helicobacter pylori, esophageal precancerous lesions, and proton pump inhibitor overuse

This article reviews the cohort study published in the World Journal of Gastroenterology , which reported low rates of Helicobacter pylori (H. pylori ) infection among esophageal cancer (EC) patients, coupled with proton pump inhibitor (PPI) overuse. These findings suggest a potential protective role of H. pylori against EC and indicate a possible association between PPI use and increased cancer risk. In light of these findings, our article examines the complex relationship between H. pylori and esophageal precancerous lesions, exploring the potential underlying mechanisms. We also address growing concerns regarding PPI overuse, including its potential effects on cancer therapy efficacy and the risk of drug interactions. Ultimately, this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SignificanceCandidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Selenium May Be Involved in Esophageal Squamous Cancer Prevention by Affecting GPx3 and FABP1 Expression: A Case-Control Study Based on Bioinformatic Analysis.

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.

Associations of Dietary Inflammatory Potential with Esophageal Precancerous Lesions and Esophageal Squamous-Cell Cancer: A Cross-Sectional Study.

Chronic inflammation plays a central role in the progression from esophageal precancerous lesions (EPLs) to esophageal squamous-cell cancer (ESCC). However, few studies have investigated the relationship between the overall inflammatory potential of diets and EPLs and ESCC. We aimed to study the association between the Dietary Inflammatory Index (DII) and EPLs and ESCC. As part of the National Cohort of Esophageal Cancer (NCEC) in China, 3967 residents (1993 men and 1974 women) aged from 40 to 69 years living in Yanting County received free gastroscopy screenings from 2017 to 2019. Dietary intake during the past year was assessed at enrollment of the cohort before screening and DII scores were calculated based on 28 food parameters. EPLs (classified into mild, moderate, and severe dysplasia) and ESCC were histologically confirmed by biopsy. Multivariable logistic regression was used to examine the associations of DII scores with EPLs and ESCC. A total of 312 participants were diagnosed with EPLs (226 with mild dysplasia, 40 with moderate dysplasia, and 46 with severe dysplasia) and 72 were diagnosed with ESCC. A statistically significant positive association was observed between DII scores and overall EPLs (ORT3 vs. T1 = 1.45, 95%CI = 1.01-2.09); the association was similar but not statistically significant for mild dysplasia (ORone-unit-increment = 1.11, 95%CI = 0.95-1.34) and for moderate and severe dysplasia combined (ORone-unit-increment = 1.15, 95%CI = 0.87-1.51). The association with ESCC was similar in magnitude but not significant, likely due to the small number of cases. In this cross-sectional study of a population in China at high risk of ESCC, DII scores were positively associated with odds of EPLs and ESCC. Consumption of anti-inflammatory foods may be beneficial to prevent EPLs and ESCC.

Exploring the Interplay Between Vitamin B12-related Biomarkers, DNA Methylation, and Gene-Nutrition Interaction in Esophageal Precancerous Lesions

Vitamin B12 depletion has been suggested to be associated with esophageal precancerous lesions (EPL). However, the potential mechanisms remain unclear. This study aims to evaluate the role of vitamin B12 and its regulated epigenetic modification in EPL and provide preliminary information on the identification of potential molecular biomarkers for the early prediction of EPL. We collected information and samples from the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 200 EPL cases and 200 matched controls. Vitamin B12, one-carbon metabolism biomarkers, genetic polymorphism of TCN2 C776G, and DNA methylation were compared. Preliminarily identified candidate promoters of differentially methylated CpG positions were further verified by targeted bisulfite sequencing. EPL cases had significantly lower serum levels of vitamin B12 and transcobalamin II, and higher serum levels of homocysteine and 5-methyltetrahydrofolate than controls. The TCN2 C776G polymorphism was found to be associated with susceptibility to EPL and may interact with vitamin B12 nutritional status to influence the risk of EPL in male subjects. In addition, global hypomethylation related to vitamin B12 depletion was observed in EPL cases, along with region-specific hypermethylation of UGT2B15 and FGFR2 promoters. This study suggests that vitamin B12 depletion may be associated with aberrant DNA methylation and increased risk of EPL through the one-carbon metabolism pathway, presents that the TCN2 C776G polymorphism may interact with vitamin B12 nutritional status to affect EPL risk in males, and also identifies specific locations in the UGT2B15 and FGFR2 promoters with potential as promising molecular biomarkers.

Prognostic value of Nrf2/HO-1 expression and its correlation with occurrence in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is thought to be started and developed by genes associated with inflammation. A cancer's ability to spread and grow can be aided by nuclear factor erythroid-2 related factor 2 (Nrf2) hyperactivation, which can also make a tumor more resistant to chemotherapy and radiation treatment. However, it is still unknown how Nrf2 gene expression affects ESCC prognosis and controls function throughout ESCC advancement. The expression of Nrf2 and HO-1 in ESCC and precancerous esophageal precancerous lesions was analyzed, and their relationship with esophageal squamous cell carcinoma was analyzed. Immunohistochemistry (IHC) was used to confirm the expression of Nrf2 and heme oxygenase-1 (HO-1) proteins in tissue microarrays from Chinese populations with ESCC. We looked at the connections between Nrf2/HO-1 expression and invading immune cells using the TIMER database. Ethnicity and N stage are associated with Nrf2 overexpression. Differentiation, N stage, vascular invasion, distant metastasis, and American Joint Committee on Cancer (AJCC) staging are all associated with HO-1 overexpression. The expression of Nrf2 and HO-1 had a favorable correlation. Patients with elevated Nrf2 and HO-1 expression had lower progression-free survival (PFS) and overall survival (OS). In high-grade intraepithelial neoplasia, Nrf2 and HO-1 expression generally occurred, partially in low-grade intraepithelial neoplasia specimens, and rarely in normal mucosa. We further show that Nrf2 suppression is linked to higher immunological marker expression and lower immune cell infiltration. The prognosis of ESCC may be improved by inhibiting the expression of Nrf2 and HO-1. A lack of immune cells was seen in ESCC with Nrf2 impairment.

Recent advances in esophageal squamous cell precancerous conditions: A review.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in many developing countries in Asia and Africa, with a 5-year survival rate of approximately 20%. Most cases are diagnosed at an advanced age when there is no effective treatment strategy. Esophageal precancerous conditions have a much better prognosis, with a 5-year survival rate of over 90% by endoscopic diagnosis and treatment. Nevertheless, limitations, contraindications, and lymph node metastasis incompetency of endoscopy. Thus, the diagnosis and treatment of esophageal precancerous lesions remain a significant challenge. Biomarker investigations provide opportunities for target detection and therapy. Additionally, drug development is ongoing. Changes in lifestyle habits, such as diet balance, smoking and alcohol cessation, are beneficial for the prognosis of esophageal precancerous lesions. Collectively, multiple and sequential diagnoses and treatments are essential for curing esophageal precancerous lesions and reducing the incidence and mortality of ESCC.

NAPRT, but Not NAMPT, Provides Additional Support for NAD Synthesis in Esophageal Precancerous Lesions.

It is hypothesized that esophageal precancerous lesions (EPLs) have a surge requirement for coenzyme I (NAD). The purpose of this study is to clarify the key control points of NAD synthesis in developing EPL by detecting related markers and the gene polymorphism of NAD synthesis and metabolism. This case-control study was conducted in Huai'an, China. In total, 100 healthy controls and 100 EPL cases matched by villages, gender, and age (±2 years) were included. The levels of plasma niacin and nicotinamide, and the protein concentration of NAMPT, NAPRT, and PARP-1 were quantitatively analyzed. PARP-1 gene polymorphism was detected to determine if the cases differed genetically in NAD synthesis. The levels of plasma niacin and nicotinamide and the concentrations of NAMPT were not related to the risk of EPL, but the over-expressions of NAPRT (p = 0.014, 0.001, and 0.016, respectively) and PARP-1 (p for trend = 0.021) were associated with the increased EPL risk. The frequency distribution of APRP-1 genotypes was found to not differ between the two groups, while the EPL group showed an increased frequency of the variant C allele. NAPRT, but not NAMPT, was found to be responsible for the stress of excess NAD synthesis in EPL. Focusing on the development of NAPRT inhibitors may be beneficial to prevent and control ESCC.

Inverse relations between Helicobacter pylori infection and risk of esophageal precancerous lesions in drinkers and peanut consumption.

BACKGROUND Helicobacter pylori (H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma (ESCC) remains a topic of much debate.AIMTo evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODSTwo hundred patients with esophageal precancerous lesions (EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTSA total of 47 (23.5%) EPL cases and 58 (29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio (OR) = 0.32, 95% confidence interval (95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection (OR = 0.39, 95%CI: 0.20-0.74).CONCLUSIONOur study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.

Progression of precancerous lesions of esophageal squamous cell carcinomas in a high-risk, rural Chinese population.

This study investigated the natural history of esophageal squamous cell carcinoma (ESCC) in rural Chinese. We sought to help provide more data to support ESCC screenings. This study was based on an existing Screening Program in Feicheng, China. Esophageal precancerous lesions were identified in 1753 cases, diagnosed from esophageal cancer screenings from 2006 to 2016. We followed up with them through endoscopic screening until October 1, 2017. Pathology results from various grades of precancerous lesions were recorded and the annual transition probabilities and incidence density of ESCC were calculated. As of October 1, 2017, a total of 4055.8 person-years has been observed. The ESCC incidence density of mild, moderate, and severe dysplasia (SD) was 0.17, 0.79, and 1.77 per 100 person-years, respectively. The median follow-up time of mild, moderate, and SD was 3.5, 2.3, and 2.2 years, respectively. The annual transition probability of mild, moderate, and SD to the next pathological level was 0.025, 0.038, and 0.016, respectively. The ESCC incidence density of males was 2.6 times higher than females (0.58 vs. 0.22), and the older age group (56-69 age group) had a ESCC incidence density 1.2 times higher than the younger group (40-55 age group) (0.45 vs. 0.39). The higher the grade of precancerous lesions, the higher the incidence density of ESCC. Screening of esophageal cancer in males and the elderly should be strengthened. It is recommended to reinforce follow-up management for untreated patients with SD/carcinoma in situ. For patients with mild and moderate dysplasia in high-risk rural Chinese populations, endoscopic follow-up intervals can be appropriately adjusted to once every 2 years.

Chinese Medicine Formula Siwu-Yin Inhibits Esophageal Precancerous Lesions by Improving Intestinal Flora and Macrophage Polarization.

Siwu-Yin (SWY), a traditional Chinese medicinal formula, can replenish blood and nourish Yin. It was recorded in ancient Chinese medicine books in treating esophageal dysphagia, which has similar symptoms and prognosis with esophageal precancerous lesions and esophageal cancer. However, its effect has not been established in vivo. This study explores the antiesophageal cancer effect of SWY on rats with esophageal precancerous lesions. By performing 16S rRNA gene sequencing and metabolomics, it was suggested that SWY may improve the composition of intestinal flora of rats by regulating the synthesis and secretion of bile acids. In addition, flow cytometry results showed that SWY treatment modified tumor microenvironment by improving macrophage polarization and therefore inhibiting the occurrence of esophageal precancerous lesions.

Influence of Oral Intaking Habit on Tongue Coating Microbiota in Patients with Esophageal Precancerous Lesions.

Background: Esophageal cancer (EC) is a common digestive tract tumor in China, and oral intaking habit has a great influence on the development of EC. The present study explored the correlation between oral intaking habit and tongue coating (TC) microbiota in patients with esophageal precancerous lesions (EPL) to provide a reasonable interpretation of the influence of oral intaking habit on microbial alterations in the EPL.Methods: A case-control study was designed with 123 EPL patients and 176 volunteers with mild esophagitis, and they were well matched using sex, age, and body mass index. The TC microbiota was profiled using high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, and the serum levels of total bile acid (TBA) and interleukin-17α (IL-17α) were measured using enzyme-linked immunosorbent assay. Alpha diversity, community structure, and linear discriminant analysis were conducted, and Spearman correlation analysis was used to build the symbiotic network.Results: No significant differences were observed in the diversity and richness of the TC microbiota between the cases and controls (P > 0.05). TC Peptostreptococcus and Capnocytophaga were enriched in EPL patients. Stratified analysis showed that TC microbial composition was affected by both EPL and oral intaking habit; for example, Atopobium and Actinomyces were positively related to oral intaking habit scores in both the cases and controls, while Simonsiella was negatively correlated with oral intaking habit status in cases but positively correlated with oral intaking habit status in controls. Although serum TBA and IL-17α were not associated with EPL (P > 0.05), the daily-drinking cases had a higher level of serum TBA than the nondrinking cases (P < 0.05), and Helicobacter pylori (Hp) negative controls had a higher level of serum TBA than the Hp-positive controls (P < 0.05). The symbiotic networks were comprised of 71 significant correlations in the controls and 52 significant correlations in the cases.Conclusions: The development of EPL changed the TC microbiota and decreased the symbiotic complexity of the TC bacteria, which were also influenced by the cancer-related oral intaking habit. Bile acid may be a key factor mediating changes in TC microbiota.

Comparative Efficacy and Safety of Anterograde vs. Retrograde Iodine Staining During Esophageal Chromoendoscopy: A Single-Center, Prospective, Parallel-Group, Randomized, Controlled, Single-Blind Trial.

Background and Aim: Chromoendoscopy with iodine staining is an important diagnostic method for esophageal carcinomas or precancerous lesions. Unfortunately, iodine staining can be associated with numerous adverse events (AEs). We found that the starting position of spraying iodine solution is likely the main reason of causing AEs. We conducted this work to determine whether clinical outcomes from anterograde iodine staining were superior to those achieved after retrograde iodine staining.Methods: A total of 134 subjects with a health risk appraisal flushing (HRA-F) score of >6 for esophageal cancer were randomly assigned to receive anterograde or retrograde iodine staining in the esophagus. The primary endpoints were the pain and the amount of iodine solution consumption. The secondary endpoints were iodine-staining effect, detection yield, and response to starch indicator.Results: Nine patients suffered from pain and six patients revealed positive response to starch indicator in retrograde iodine-staining group; however, no patient reported pain (0/67) and all patients revealed a negative response to starch indicator in anterograde iodine-staining group. The amount of iodine solution consumption in anterograde iodine-staining group (4.97 mL) was significantly lower than that (6.23 mL) in retrograde iodine-staining group; however, the iodine-staining effect and detection yield were comparable between the two groups.Conclusions: Anterograde iodine staining during Lugol chromoendoscopy appears to be as effective, but significantly safer than retrograde iodine staining.

820 EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA AND PRECANCEROUS LESIONS

Abstract With the development of endoscopic technology, endoscopic mucosal dissection (ESD) has become one of the standard treatments for superficial esophageal squamous cell carcinoma and precancerous lesion (SESCC-PL). However, the efficacy and safety of ESD in some special SESCC-PL patients is still unclear. The purpose of this study was to analyze the efficacy and safety of ESD in patients with SESCC-PL, especially for some special patients. Methods Firstly, according to the depth of lesions, all patients were divided into three groups: the epithelium and lamina propria group (M1-M2), the muscularis mucosae and submucosal superficial layer group (M3-SM1) and the submucosal deep layer group (≥SM2). Secondly, according to the age of patients, all patients were divided into two groups: elderly group (≥ 65 years old) and non-elderly group (&amp;lt;65 years old). Finally, all patients were divided into two groups: patients with liver cirrhosis group and patients without liver cirrhosis group. The efficacy and safety of ESD for these patients were analyzed. Results There was no significant difference in operation time, resection speed, en bloc resection rate, bleeding rate, muscularis propria injury rate, perforation rate and intraoperative esophageal stricture rate in three groups with different depths of lesion. However, the R0 resection rate among the three groups decreased with the increase of lesion depth (P &amp;lt; 0.001). There was no significant difference in all surgical indexes between the non-elderly group and the elderly group (all P &amp;gt; 0.05). And there was also no significant difference in all surgical indexes including bleeding rate between the patients with liver cirrhosis and without liver cirrhosis (all P &amp;gt; 0.05). Conclusion This study proved that ESD is safe and effective for all kinds of patients with SESCC-PL, especially for patients with lesion depth ≥ M3, elderly patients and patients with liver cirrhosis, ESD can still achieve a satisfactory treatment effect and a good survival prognosis. Liver cirrhosis is not a contraindication to ESD.

Characterization of the Oral and Esophageal Microbiota in Esophageal Precancerous Lesions and Squamous Cell Carcinoma

Important evidence indicates that the microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). Here, paired saliva and brush specimens were obtained from 276 participants undergoing upper gastrointestinal endoscopic examination before or during screening for upper gastrointestinal (UGI) cancer. The esophageal microbiota was investigated by 16S rRNA gene profiling and next-generation sequencing. We observed that as the disease progressed, the α diversity in the saliva and cell brush samples decreased. Linear discriminant analysis effect size (LEfSe) results showed that in both the saliva and cell brush specimens, Granulicatella, Rothia, Streptococcus, Gemella, Leptotrichia and Schaalia were common biomarkers in patients with low-grade dysplasia, Lactobacillus was a common biomarker in patients with high-grade dysplasia, and Bosea, Solobacterium, Gemella, and Peptostreptococcus were common biomarkers in patients with esophageal cancer. The top 3 genera in the saliva and cell brush specimens had areas under the curve (AUCs) of 87.16 and 89.13%, respectively, to distinguish ESCC patients from normal people. The PICRUSt2 results identified in brush samples that patients with ESCC had decreased nitrate reductase functions. Our results suggest that future studies can focus on the function of the characteristic bacteria in ESCC.

DNA polymerase β deficiency promotes the occurrence of esophageal precancerous lesions in mice

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase β (Polβ), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polβ is related to the occurrence of esophageal cancer, but the role of Polβ deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polβ-knockout mice were used to explore the relationship of Polβ deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polβ-KO mice were more serious than those in Polβ-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polβ increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polβ-KO mice. We also found that deletion of Polβ promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polβ knockout promotes the occurrence of esophageal precancerous lesions.

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Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase β (Polβ), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polβ is related to the occurrence of esophageal cancer, but the role of Polβ deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polβ-knockout mice were used to explore the relationship of Polβ deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polβ-KO mice were more serious than those in Polβ-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polβ increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polβ-KO mice. We also found that deletion of Polβ promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polβ knockout promotes the occurrence of esophageal precancerous lesions.

Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenya

BackgroundExposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot. ObjectiveTo evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions. MethodsWe recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol’s chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD. ResultsPAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4–28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01–17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD. ConclusionsUrinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.

Vitamin B12 may play a preventive role in esophageal precancerous lesions: a case-control study based on markers in blood and 3-day duplicate diet samples.

It is hypothesized that vitamin B12 may prevent tumor initiation during the early stage of carcinogenesis such as esophageal precancerous lesions (EPL), whereas an excessive level may promote tumor progression during the later stages of carcinogenesis. This study aimed to determine the role of vitamin B12 in EPL by detecting vitamin B12-related markers in both blood and diet. This case-control study based on 3-day duplicated diet samples was conducted in a high-risk area of Huai'an, China. A 100 EPL cases and 100 healthy controls matched by gender, age (± 2years) and villages were included. Dietary intake of vitamin B12 and cobalt, plasma cobalt level, the serum levels of vitamin B12 and transcobalamin II (TC II) were quantitatively analyzed. Dietary vitamin B12 intake (p for trend = 0.384) and plasma cobalt level (p for trend = 0.253) were not associated with EPL risk, but high dietary cobalt intake (p for trend = 0.034), increased serum levels of vitamin B12 (p for trend = 0.036) and TC II (p for trend < 0.001) were significantly associated with the reduced EPL risk. However, the significant negative association between dietary cobalt intake, plasma cobalt level or serum vitamin B12 level and EPL was only found in female or male subjects. Excellent transport capability of bio-active vitamin B12 in vivo and adequate levels of vitamin B12 and cobalt may play preventive roles in EPL. Additionally, the association between vitamin B12, cobalt and the risk of EPL may vary in different genders.

Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and precancerous lesions

BackgroundThis study evaluated gene-nutrition interactions between folate and the aberrant DNA methylation of tumor suppressor genes in different stages of carcinogenesis of esophageal squamous cell carcinoma (ESCC).MethodsTwo hundred ESCC cases, 200 esophageal precancerous lesion (EPL) cases, and 200 controls matched by age (± 2 years) and gender were used for this study. Baseline data and dietary intake information was collected via questionnaire. The serum folate levels and methylation status of promoter regions of p16 and p53 were detected.ResultsThe interactions of increased serum folate level with unmethylated p16 and p53 promoter regions were significantly associated with a reduced risk of both EPL and ESCC (p for interaction < 0.05). The interactions of the lowest quartile of serum folate level with p16 or p53 methylation was significantly associated with an increased risk of ESCC (OR = 2.96, 95% CI, 1.45–6.05; OR = 2.34, 95% CI, 1.15–4.75). An increased serum folate level was also related to a decreasing trend of EPL and ESCC risks when p16 or p53 methylation occurred. The interaction of spinach, Chinese cabbage, liver and bean intake with unmethylated p16 and p53 was significantly associated with a reduced risk of EPL or ESCC (p for interaction < 0.05).ConclusionsThe interactions between a high folate level and unmethylated p16 and p53 promoter regions may have a strong preventive effect on esophageal carcinogenesis. Additionally, a high folate level may offset the tumor-promoting effects of aberrant DNA methylation of the genes, but it is also noteworthy that a very high level of folate may not have a protective effect on EPL in some cases.