Risk Factors For Esophageal Squamous Cell Carcinoma Research Articles

A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

EsophaCap Sponge Cytology Screening for Esophageal Squamous Cell Dysplasia and Carcinoma is Feasible in a High-Risk Area in Western India

Objective: Conventional endoscopy remains the gold standard for detecting esophageal squamous cell carcinoma (ESCC) despite its high cost and need for expertise. In resource-poor regions, a less labor-intensive yet accurate screening tool is needed. The purpose of this study is to assess feasibility of establishing a non-endoscopic screening program in rural India and to test the diagnostic accuracy of the EsophaCap swallowable sponge in detecting ESCC in a high-risk patient population. Methods: A prospective cohort study was conducted between 2017 and 2019, in which subjects with risk factors for ESCC (tobacco smoking or chewing, betel nut/leaf, alcohol and hot beverage consumption) were approached during upper endoscopy visits at a clinic in Western India. After obtaining EsophaCap sponge cytology samples, random endoscopic biopsies were obtained at 20 and 30 cm from the incisors. Histologic diagnoses were confirmed and select biopsy samples were sequenced for genomic aberrations. Visual Analog Scale (VAS) scores were used to assess patient experience of sponge swallowing (range 1-5, “very comfortable” to “very uncomfortable”). Results: In our cohort of 178 patients, 157 (88%) were males. Mean age was 52 ± 12 years. Sixty-eight (38%) patients were current cigarette or bidi smokers; 132 (74%) patients were daily tobacco chewers, and 83 (47%) patients chewed betel nuts/leaves on a daily basis. Forty-six (26%) patients were daily alcohol users and 151 (85%) patients drank ≥3 hot beverages per day. The median number of risk factors per patient was 3. The first-time swallow rate of the encapsulated sponge was successful in 190/200 (95%) patients. Median VAS score was 2 (“comfortable”). EsophaCap cytology revealed 6 (3%) patients with atypical squamous cells of unknown significance (ASCUS) and 3 (1%) patients with dysplasia. Based on the endoscopic biopsies, 6 (3%) patients had ESCC, 4 (2%) patients had lesions with squamous dysplasia, and 63 (35%) patients had esophageal leukoplakia. Four patients classified as ASCUS pathology via EsophaCap were normal, benign, or leukoplakia via endoscopy. EsophaCap’s sensitivity and specificity for detecting dysplasia or ESCC by histology was 30% and 97%, respectively. Conclusions: Establishing a non-endoscopic screening program in a high-risk area with language barriers and low medical literacy is very safe and feasible. EsophaCap may help identify ASCUS patients in need of serial endoscopic monitoring. Further studies of combined sponge cytology with immunohistochemistry studies are necessary to improve accuracy of ESCC screening.

Epidemiology of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a leading cause of death worldwide, particularly prevalent in Southern and Eastern Africa, and central Asia. Initial studies identified various factors associated with an increased risk of ESCC, leading to subsequent research investigating the underlying biological mechanisms. This narrative review aims to summarize the role of risk factors in ESCC development and propose future research directions. A systematic literature search was conducted using EMBASE, MEDLINE/PubMed, and CENTRAL databases to identify relevant publications. Included studies updated the epidemiology of ESCC, including the incidence, prevalence and mortality and its variations globally. We reported on socio-demographic impact on these geographic variations. We, then, focused on identifying risk factors associated with ESCC. The identified risk factors were categorized into 5 subcategories: smoking, alcohol, dietary factors, environmental factors and infection. Each subcategory’s risk factors were summarized and explored, providing geographical links for these associations. The review emphasizes the current understanding of several risk factors for ESCC, and specifically makes geographical links, and potential explanations for their associations were explored. However, further research is essential to validate these findings and gain insights into their impact on tumor biology.

Metabolomic transition trajectory and potential mechanisms of N-nitrosomethylbenzylamine induced esophageal squamous cell carcinoma in rats.

Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD+ in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.

Exploiting the Molecular Basis of Oesophageal Cancer for Targeted Therapies and Biomarkers for Drug Response: Guiding Clinical Decision-Making.

Worldwide, oesophageal cancer is the sixth leading cause of deaths related to cancer and represents a major health concern. Sub-Saharan Africa is one of the regions of the world with the highest incidence and mortality rates for oesophageal cancer and most of the cases of oesophageal cancer in this region are oesophageal squamous cell carcinoma (OSCC). The development and progression of OSCC is characterized by genomic changes which can be utilized as diagnostic or prognostic markers. These include changes in the expression of various genes involved in signaling pathways that regulate pathways that regulate processes that are related to the hallmarks of cancer, changes in the tumor mutational burden, changes in alternate splicing and changes in the expression of non-coding RNAs such as miRNA. These genomic changes give rise to characteristic profiles of altered proteins, transcriptomes, spliceosomes and genomes which can be used in clinical applications to monitor specific disease related parameters. Some of these profiles are characteristic of more aggressive forms of cancer or are indicative of treatment resistance or tumors that will be difficult to treat or require more specialized specific treatments. In Sub-Saharan region of Africa there is a high incidence of viral infections such as HPV and HIV, which are both risk factors for OSCC. The genomic changes that occur due to these infections can serve as diagnostic markers for OSCC related to viral infection. Clinically this is an important distinction as it influences treatment as well as disease progression and treatment monitoring practices. This underlines the importance of the characterization of the molecular landscape of OSCC in order to provide the best treatment, care, diagnosis and screening options for the management of OSCC.

Risk Factors for Esophageal Squamous Cell Carcinoma in Patients with Head and Neck Squamous Cell Carcinoma

Background Esophageal squamous cell carcinoma (ESCC) is a common second primary neoplasia in patients with a history of head and neck squamous cell carcinoma (HNSCC). The aim of this study was to provide further information and novel insights into the risk factors for ESCC in patients with HNSCC. Methods We retrospectively analyzed 98 HNSCC patients diagnosed from 2007 to 2017, 30 HNSCC patients suffering from ESCC, who had undergone endoscopic examination because of positive imaging examinations or symptoms, and 68 HNSCC patients who had no ESCC occurrence for at least six years post-HNSCC diagnosis. Associated clinicopathological data and lifestyle information of the ESCC group and the without ESCC group were collected, and a case-control study of risk factors was analyzed between the two groups. Results The majority (83.4%) of the cases with HNSCC esophageal cancers were male patients over 50 years. We established that 93.75% (30/32) of the ESCC occurred within six years after HNSCC diagnosis. HNSCC location, stage, and radiotherapy history had no significant association with the development of ESCC. High Ki67 labeling index (Ki67 LI) (>46) patients tended to be 3.1 times (95% CI = 1.3–7.6) more likely to develop ESCC compared to low Ki67 LI (≤45) patients (P < 0.05). Drinkers with alcohol flushing response were at a 3.3 times higher risk to have ESCC (95% CI = 1.0–10.4) than drinkers without flush response (P < 0.05). Conclusions HNSCC patients, especially drinkers with an alcohol flushing response, as well as those with high Ki67 LI of HNSCC tissue, were more likely to develop ESCC.

Risk Stratification and Validation of Eleven Autophagy-Related lncRNAs for Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC), the most prevalent subtype of esophageal cancer, ranks sixth in cancer-related mortality, making it one of the deadliest cancers worldwide. The identification of potential risk factors for ESCC might help in implementing precision therapies. Autophagy-related lncRNAs are a group of non-coding RNAs that perform critical functions in the tumor immune microenvironment and therapeutic response. Therefore, we aimed to establish a risk model composed of autophagy-related lncRNAs that can serve as a potential biomarker for ESCC risk stratification. Using the RNA expression profile from 179 patients in the GSE53622 and GSE53624 datasets, we found 11 lncRNAs (AC004690.2, AC092159.3, AC093627.4, AL078604.2, BDNF-AS, HAND2-AS1, LINC00410, LINC00588, PSMD6-AS2, ZEB1-AS1, and LINC02586) that were co-expressed with autophagy genes and were independent prognostic factors in multivariate Cox regression analysis. The risk model was constructed using these autophagy-related lncRNAs, and the area under the receiver operating characteristic curve (AUC) of the risk model was 0.728. To confirm that the model is reliable, the data of 174 patients from The Cancer Genome Atlas (TCGA) esophageal cancer dataset were analyzed as the testing set. A nomogram for ESCC prognosis was developed using the risk model and clinic-pathological characteristics. Immune function annotation and tumor mutational burden of the two risk groups were analyzed and the high-risk group displayed higher sensitivity in chemotherapy and immunotherapy. Expression of differentially expressed lncRNAs were further validated in human normal esophageal cells and esophageal cancer cells. The constructed lncRNA risk model provides a useful tool for stratifying risk and predicting the prognosis of patients with ESCC, and might provide novel targets for ESCC treatment.

Association of Esophageal Squamous Cell Carcinoma With the Interaction Between Poor Oral Health and Single Nucleotide Polymorphisms in Regulating Cell Cycles and Angiogenesis: A Case-Control Study in High-Incidence Chinese

IntroductionOral health and genetic factors can independently influence the risk of developing esophageal squamous cell carcinoma (ESCC).ObjectivesThe primary objective of this study was to investigate the interactive effects of oral health and genetic factors on ESCC risk.MethodsThis was a matched case-control study with 927 ESCC patients and 1701 matched controls. We selected 101 candidate single nucleotide polymorphisms (SNPs) from 59 genes that were associated with ESCC. Oral health was assessed based on tooth-brushing frequency, tooth loss, and age at the time of first tooth loss. An unconditional logistic regression model was employed in which SNP–oral health interactions were assessed as risk factors for ESCC, after adjusting for age and sex. A genetic risk score (GRS) analysis was conducted.ResultsThe association between GRS and ESCC and the synergistic effect of GRS and oral health on ESCC were examined. Daily frequency of tooth-brushing was found to interact with 5 SNPs, rs3765524, rs753724, rs994771, rs3781264, and rs11187842, to increase the risk of ESCC. In particular, individuals with genotype TT of rs3765524 who brushed their teeth less than twice a day had a 5.13-times higher risk of ESCC than those with genotype CC who brushed their teeth at least twice a day. Furthermore, tooth loss interacted with two SNPs: rs1159918 from ADH1B and rs3813867 from CYP2E1.ConclusionOral health may interact with genetic factors increasing ESCC risk, which provides new insights into the relationship between ESCC and gene–lifestyle interactions which can be used for disease prevention.

Outcomes of Esophageal Cancer after Esophagectomy in the Era of Early Injection Laryngoplasty.

(1) Background: severe weight loss was reported to be related to unilateral vocal fold paralysis (UVFP) after esophagectomy and could thus impair survival. Concomitant radical lymph node dissection along the recurrent laryngeal nerve during esophageal cancer surgery is controversial, as it might induce UVFP. Early intervention for esophagectomy-related UVFP by administering intracordal injections of temporal agents has recently become popular. This study investigated the survival outcomes of esophagectomy for esophageal squamous cell carcinoma (ESCC) after the introduction of early injection laryngoplasty (EIL). (2) Methods: a retrospective review of patients with ESCC after curative-intent esophagectomy was conducted in a tertiary referral medical center. The necessity of EIL with hyaluronic acid was comprehensively discussed for all symptomatic UVFP patients. The survival outcomes and related risk factors of ESCC were evaluated. (3) Results: among the cohort of 358 consecutive patients who underwent esophagectomy for ESCC, 42 (11.7%) showed postsurgical UVFP. Twenty-nine of them received office-based EIL. After EIL, the glottal gap area, maximum phonation time and voice outcome survey showed significant improvement at one, three and six months measurements. The number of lymph nodes in the resected specimen was higher in those with UVFP than in those without UVFP (30.1 ± 15.7 vs. 24.6 ± 12.7, p = 0.011). The Kaplan–Meier overall survival was significantly better in patients who had UVFP (p = 0.014), received neck anastomosis (p = 0.004), underwent endoscopic resection (p < 0.001) and had early-stage cancer (p < 0.001). Multivariate Cox logistic regression analysis showed two independent predictors of OS, showing that the primary stage and anastomosis type are the two independent predictors of OS. (4) Conclusion: EIL is effective in improving UVFP-related symptoms, thus providing compensatory and palliative measures to ensure the patient’s postsurgical quality of life. The emerging use of EIL might encourage cancer surgeons to radically dissect lymph nodes along the recurrent laryngeal nerve, thus changing the survival trend.

Missing and decayed teeth, oral hygiene and dental staining in relation to esophageal cancer risk: ESCCAPE case-control study in Kilimanjaro, Tanzania.

In the African esophageal squamous cell carcinoma (ESCC) corridor, recent work from Kenya found increased ESCC risk associated with poor oral health, including an ill‐understood association with dental fluorosis. We examined these associations in a Tanzanian study, which included examination of potential biases influencing the latter association. This age and sex frequency‐matched case‐control study included 310 ESCC cases and 313 hospital visitor/patient controls. Exposures included self‐reported oral hygiene and nondental observer assessed decayed+missing+filled tooth count (DMFT index) and the Thylstrup‐Fejerskov dental fluorosis index (TFI). Blind to this nondental observer TFI, a dentist independently assessed fluorosis on photographs of 75 participants. Odds ratios (ORs) are adjusted for demographic factors, alcohol and tobacco. ESCC risk was associated with using a chewed stick to brush teeth (OR 2.3 [95% CI: 1.3‐4.1]), using charcoal to whiten teeth (OR 2.13 [95% CI: 1.3, 4.1]) and linearly with the DMFT index (OR 3.3 95% CI: [1.8, 6.0] for ≥10 vs 0). Nondental observer‐assessed fluorosis was strongly associated with ESCC risk (OR 13.5 [95% CI: 5.7‐31.9] for TFI 5+ v 0). However, the professional dentist's assessment indicated that only 43% (10/23) of participants assessed as TFI 5+ actually had fluorosis. In summary, using oral charcoal, brushing with a chewed stick and missing/decayed teeth may be risk factors for ESCC in Tanzania, for which dose‐response and mechanistic research is needed. Links of ESCC with “dental fluorosis” suffered from severe exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining or reverse causality.

Clinical significance of HDAC1, -2 and -3 expression levels in esophageal squamous cell carcinoma.

The present study analyzed the expression of the histone deacetylase (HDAC) 1, 2 and 3 in primary esophageal squamous cell carcinoma (ESCC) samples and how their levels correlate with clinicopathological parameters. ESCC patients (n=88) in the present study had received no previous treatment before undergoing surgical excision. The mRNA expression of HDAC1, -2 and -3 were detected by semi-quantified PCR in ESCC samples and distal normal samples. The relationship of HDAC1, -2 and -3 expression with clinicopathological parameters was analyzed by χ2 test. The correlation among these HDACs was analyzed by Pearson's correlation test. Compared with distal normal tissues, ESCC samples had higher expression of HDAC1, but not HDAC2 or HDAC3 (P<0.05). The expression of HDACs was different between Kazak and Han ethnicities. The expression of HDAC2 was correlated with invasion depth (P<0.05), but not with sex, age, metastasis, or the degree of tumor differentiation (P>0.05). There was no association between HDAC1 or HDAC3 and clinicopathological parameters (P>0.05). For the Kazak and Han ethnicities, HDAC1 expression was present in male patients, patients with well/moderate differentiated ESCC and T3 and T4 ESCC (P<0.01). HDAC1 in patients aged <60 was associated with ethnicity (P<0.05). HDAC2 expression was different in positive LN metastasis, well/moderate differentiation and T3 and T4 ESCC (P<0.01). HDAC3 expression in male patients, patients with negative LN metastasis and well/moderate differentiation ESCC was associated with ethnicity (P<0.05). Additionally, the expression levels of HDAC1, -2 and -3 did not correlate with each other. Thus, HDAC1 expression may be used as a risk factor for ESCC and HDAC2 levels may be used to predict invasion depth. The expression of HDAC1, -2 and -3 has ethnic differences.

Associations Between Gastric Atrophy and Its Interaction With Poor Oral Health and the Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Region of China: A Population-Based Case-Control Study.

Previous findings concerning gastric atrophy as a potential risk factor for esophageal squamous cell carcinoma (ESCC) have been inconsistent. We aimed to test whether gastric atrophy and, further, its interaction with poor oral health elevated the risk of ESCC in a high-risk region of China. Our population-based case-control study in Taixing, China (2010–2014), recruited cases from local hospitals and the local cancer registry. Controls were selected randomly from the local population registry. Ultimately, 1,210 cases and 1,978 controls answered questionnaires and provided blood samples for assay of pepsinogens. Unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. Gastric atrophy (defined as a serum level of pepsinogen I of <55 μg/L) was associated with an increased risk for ESCC (odds ratio = 1.61; 95% confidence interval: 1.33, 1.96), even after full adjustment for potential confounding factors. In addition, suggestion of an additive interaction between gastric atrophy and poor oral health was observed (relative excess risk due to interaction = 1.28, 95% confidence interval: 0.39, 2.18). We conclude that gastric atrophy appears to be a risk factor for ESCC in a high-risk region of China, and there is a suggested additive interaction with poor oral health that increases this risk even further.

A nomogram for endoscopic screening in a high esophageal squamous cell cancer risk area: results from a population-based study.

BackgroundEndoscopy is the main approach used for esophageal squamous cell carcinoma (ESCC) screening, especially in high-risk areas. However, little consensus has been achieved in recent ESCC screening programs, and endoscopists have selected patients only by age and family history.Patients and methodsTo generate a proper strategy for selecting an eligible population for endoscopic screening based on demographic factors, lifestyle, and eating habits, a total of 7,830 residents in an area with a high risk of ESCC were recruited for this study. All participants underwent endoscopic examinations that were conducted by experienced endoscopists. Risk factors for ESCC and other lesions were selected by univariate and multivariate logistic regressions. A nomogram for the prediction of ESCC and premalignant lesions was constructed, which included information on age, sex, occupation, labor intensity, income, and mining exposure. Receiver operating characteristic (ROC) curve analysis was performed to present the predictive accuracy of the nomograms.ResultsThe area under the curve (95% CI) was 0.749 (0.711–0.788) for this nomogram. By applying this nomogram, we could exclude 60% (4704/7830) of patients before endoscopy screening and detect all ESCC cases as well as most esophageal lesions in the remaining population.ConclusionIn conclusion, we provided a ready-to-use preclinical tool with the potential to select eligible people with high risk of ESCC for endoscopy screening.

PS02.157: ESOPHAGEAL SQUAMOUS CELL CARCINOMA IS ASSOCIATED WITH CHRONIC DISEASES AS WELL AS UNHEALTHY LIFESTYLES

Abstract Background Cancer and other chronic diseases such as cardiovascular disease, diabetes, chronic kidney disease, and respiratory disease share common risk factors, including aging and unhealthy lifestyles (eg, smoking and alcohol misuse). Although the recent prospective cohort large-scale study showed chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death, the relation between esophageal squamous cell carcinoma (ESCC) and non-cancer chronic diseases (NCCD) still remain unknown. The aim of this study is to assess the independent and joint associations of major NCCD and ESCC. Methods From April 2011 to March 2017, 406 consecutive patients with ESCC diagnosed pathologically were enrolled. Their medical records as to patients’ background, the reason for their consultation, lifestyles, and medical history were investigated retrospectively in detail. Results As to the reason for their consultation, 45 patients (25.3%) were diagnosed at annual medical checkup (no symptoms), 125 (70.2%) consulted a doctor for any symptoms such as dysphagia, and 8 (4.5%) had other reasons. As to lifestyles, 304 (78.1%) were drinkers of alcohol (daily amount of alcohol consumption &gt; 20g) and 302 (77.4%) were smokers (Brinkman index &gt; 200), respectively. As to the medical history related to cancer or gastrointestinal diseases, 25 (6.8%) had a history of laryngopharyngeal cancer, 20 (5.1%) had a history of gastric cancer, 2 (0.5%) had a history of breast cancer, one (0.3%) had a history of sclerodema, and one (0.3%) had a history of esophageal achalasia. Of the 406 ESCC patients, 305 were early ESCC and the remaining 101 were advanced ESCC. As to the medical history in patients with advanced ESCC, 22 (21.8%) had a history of cancer of other organs, and 48 (47.5%) had NCCD including hypertension (35 patients), diabetes (18 patients), and hyperlipidemia (12 patients). Conclusion NCCD is an overlooked risk factor for ESCC, as important as two major lifestyle factors combined (drinkers of alcohol and smokers). General physicians who follow up NCCD patients should pay attention to the coexistence of ESCC. Disclosure All authors have declared no conflicts of interest.

Endoscopic treatment of early esophageal squamous neoplasia.

Esophageal squamous cell carcinoma (ESCC) remains the most common esophageal cancer in the world, though a rising incidence of esophageal adenocarcinoma could be seen during the last decade in the western world. There are several known risk factors for ESCC, such as smoking, alcohol consumption, radiation or others. As there is a risk of lymph node metastasis already in early stages, early endoscopic detection is crucial for curative endoscopic treatment options. Therefore, newest technical improvements such as enhancement techniques or virtual chromoendoscopy are helpful for the diagnosis of mucosal carcinoma. Lugol's iodine remains the gold standard to detect early esophageal cancer, however, it should be combined with these newer techniques. For the prediction of invasion depth, a new classification was developed by the Japan Esophageal society. By using magnifying endoscopy and Narrow Band Imaging, the microvascular morphology allows a prediction of invasion depth of early squamous cell carcinoma. Endoscopic resection is suitable for patients with early-stage ESCC (m1-m2), because of the low risk of lymph node metastasis. EMR should be performed if the lesion is smaller than 15 mm, because a R0 resection can be achieved. Larger lesions (>15 mm) should be resected via endoscopic submucosal dissection to reach an en bloc resection, a lower recurrence rate and a R0 situation.

Epidemiology of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of the 456,000 incident esophageal cancers each year. Regions of high incidence include Eastern to Central Asia, along the Rift Valley in East Africa, and into South Africa. There are many causes of ESCC, which vary among regions. Early studies in France associated smoking cigarettes andheavy alcohol consumption with high rates of ESCC, but these factors cannot explain the high incidence in other regions. We discuss other risk factors for ESCC, including polycyclic aromatic hydrocarbons from a variety of sources, high-temperature foods, diet, and oral health and the microbiome-all require further research. A growing list of defined genomic regions affects susceptibility, but large genome-wide association studies have been conducted with ethnic Chinese subjects only; more studies are called for in the rest of Asiaand Africa. ESCC has been understudied, but growing infrastructure in more high-incidence countries will allow rapid progress in our understanding.

Association of TP53 codon 72 genotype polymorphism and environmental factors with esophageal squamous cell carcinoma in the Mongolian population of the Chinese region of Inner Mongolia

The present study analyzed the association of tumor protein p53 (TP53) Pro72Arg polymorphism with esophageal squamous cell carcinoma (ESCC) in the Mongolian population of Tongliao (Inner Mongolia, China). Restriction fragment length polymorphism-polymerase chain reaction was used to detect the genotype distribution of TP53 Pro72Arg polymorphism in 100 patients with ESCC and 50 healthy controls from the same population. Besides, the correlation between ESCC in Mongolian patients and various factors such as age, sex, cigarette smoking and alcohol consumption was analyzed. χ2 test revealed significant associations between alcohol consumption (P=0.00006) and cigarette smoking (P=0.00076) and ESCC in Mongolian patients. Notably, the Pro72 allele was significantly enriched in patients with ESCC compared with its abundance in the healthy control group, and the genotype of Pro/Arg on p53 codon 72 was confirmed to exhibit a significant correlation with ESCC in Mongolian patients. The present study demonstrated that alcohol drinking and cigarette smoking were risk factors for ESCC in the Mongolian population. Mongolian patients who carry the partocular genotype of Arg/Pro or Pro/Pro on p53 codon 72 may be more likely to develop ESCC. Compared with the p53 codon 72 genotype Arg/Arg, the TP53 Pro72 allele increased the risk of ESCC in Mongolian patients by 1.659-fold.

Single Nucleotide Polymorphisms in the PTPN1 Gene Are Associated with Susceptibility to Esophageal Squamous Cell Carcinoma: A Case-Control Study in Inner Mongolia, China.

This case-control study investigated the association of single nucleotide polymorphisms in the PTPN1 gene with susceptibility to esophageal squamous cell carcinoma (ESCC) in Inner Mongolia, China. A total of 302 patients living in Inner Mongolia China who were pathologically diagnosed with ESCC between April 2012 and 2016 were selected for the ESCC group; 373 healthy individuals were selected for the control group. The rs2904268 C>G, rs2230605 A>G, and rs16995309 C>T polymorphisms in the PTPN1 gene were detected by bidirectional polymerase chain reaction amplification of specific alleles. The haplotype frequencies were analyzed by SHEsis software. Binary logistic regression analysis was conducted to analyze risk factors associated with ESCC. Statistical differences between the ESCC and control groups were observed for history of smoking, drinking, and poor eating habits (all p < 0.05). Both the rs2904268 C>G CG and GG genotype frequencies were markedly higher in the ESCC group relative to the control group (both p < 0.05). However, the genotype frequencies of rs2230605 A>G and rs16995309 C>T were similar between the ESCC and control groups (all p > 0.05). Compared with the control group, the ESCC group had notably elevated frequencies of the GGC and GAT haplotypes and significantly reduced frequencies of CGC and GGT haplotypes (all p < 0.05). A history of smoking, drinking, poor eating habits, the rs2904268 C>G CG+GG genotypes, and the GAT haplotype were all identified as risk factors for ESCC (all p < 0.05). These results indicated that the PTPN1 gene polymorphism rs2904268 is associated with susceptibility to ESCC in Inner Mongolia.

Joint Effects of Low Body Mass Index and Alcohol Consumption on Developing Esophageal Squamous Cell Cancer: a Korean Nationwide Population-Based Cohort Study

Objective:In Korea, 95% of esophageal cancer (EC) was the squamous cell-type. We sought to determine the combined risk of alcohol consumption on developing esophageal squamous cell carcinoma (ESCC) in pre-diagnostic underweight subjects using Korean national data.Methods:We analyzed the clinical data from a total of 264,084 individuals aged 40 years or older, who received healthcare checkups arranged by the national insurance program, between 2003 and 2008 in Korea. Cox proportional hazards regression was used after adjusting confounding factors.Result:Newly diagnosed 278 EC was identified using the claims data during a median follow-up duration of 7.9 years. It was determined that underweight and obesity-compared with normal weight-were significantly associated with 73% increased risk and 30% decreased risk of EC, respectively. Weight gain reduced the risk of EC. Alcohol consumption increased risk for EC in a dose-dependent manner. Heavy alcohol consumption in individuals with underweight increased the risk of developing EC dramatically.Conclusion:Underweight was a risk factor for ESCC and alcohol consumption raised the risk synergistically with low BMI. Achieving normal range of BMI could reduce the risk of ESCC.

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population.

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TLSNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P < 0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P < 0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84-3.14), 1.36 (1.03-1.79), 1.01 (0.76-1.35), and 1.37 (1.03-1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.