Risk Of Esophageal Squamous Cell Carcinoma Research Articles

Risk Factors Related to Esophageal Cancer, a Case-Control Study in Herat Province of Afghanistan.

The Herat province of Afghanistan is located on the Asian Esophageal Cancer Belt (AECB), a wide area in Central and Eastern Asia where very high rates of esophageal cancer (EC) have been observed. Several risk factors have been reported in the AECB Region by previous studies. Considering lack of information in Afghanistan on this issue, a study was conducted to determine the major risk factors related to EC in order to guide protective measures. A population-based case-control study was performed from July 2015 to August 2016 among 657 EC patients in the Herat Province and 180 histopathological confirmed cases and 189 controls were interviewed. A structured questionnaire was used and face-to-face interviews were conducted. Low body mass index (BMI), low socio-economic status, family history of EC, consumption of dark tea, very hot beverage and qulurtoroosh were found to be statistically significant for EC and esophageal squamous cell carcinoma (ESCC) in univariate analyses. According to multivariate analyses, sex (OR=2.268; 95% CI=1.238-4.153), very hot beverages (OR=2.253; 95% CI=1.271- 3.996), qulurtoroosh (OR=5.679; 95% CI=1.787-18.815), dark tea (OR=2.757; 95% CI=1.531-4.967), high previous BMI (OR=0.215; 95% CI=0.117-0.431) and low socio-economic status (OR=1.783; 95% CI=1.007-3.177) were associated with ESCC. Being male was found to increase the risk of ESCC with OR=2.268 (95% CI=1.238-4.153). Consuming very hot beverages dark tea and a local food, qulurtoroosh, were found as important risk factors for EC. Our findings warrant further studies and necessitate the implementation of protective measures for EC which is one of the leading cancers in the region.

Relationship between esophageal squamous cell carcinoma risk and ALDH2 and ADH1B polymorphisms:Evidence from a Meta-Analysis

Relationship between esophageal squamous cell carcinoma risk and ALDH2 and ADH1B polymorphisms:Evidence from a Meta-Analysis

325. THE ASSOCIATED RISK BETWEEN SINGLE NUCLEOTIDE POLYMORPHISMS OF AP1S1 AND ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN CHINESE POPULATION

Abstract The σ1A subunit of the adaptor protein 1 (AP1S1) participates in intracellular transport pathways, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case–control study, we investigated the genetic susceptibility to esophageal squamous cell carcinoma (ESCC) in relation to Single Nucleotide Polymorphisms (SNPs) of AP1S1 among Chinese population and made a preparation for the subsequent esophageal SNP risk model building. A database containing a total of 1143 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P < 0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step. AP1S1 rs77387752 C > T mutated homozygous TT was an independent risk factor for ESCC, while SNP rs4729666 C > T and rs35208462 C > T mutated heterozygote TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers. These three AP1S1 SNP sites could be incorporated into subsequent SNPs risk models for ESCC in specific populations. AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers. These SNP sites might be added into the building of risk model and then the early diagnosis of ESCC. Besides, further mechanical exploration is required. Table. Logistic regression analyses of associations between AP1S1 SNPs rs77387752 C > T, rs4729666 C > T, rs35208462 C > T and risk of ESCC.

Household air pollution, polycyclic aromatic hydrocarbons and esophageal cancer risk in Kenya: ESCCAPE case-control study

Background and Aim Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Western Kenya. Established risk factors (e.g. smoking and alcohol consumption) are not common in female patients. Exposure to household air pollution (HAP) from solid fuels used for cooking and heating might be relevant in ESCC aetiology. As such, this study aims to examine the relationship between self-reported indicators of exposure to HAP with risk of ESCC in Western Kenya. Methods Six-hundred and four (604) ESCC cases and six-hundred and thirty-one (631) controls were recruited during three phases of the ESCCAPE Kenya case-control study. Surveys on risk factors were conducted with all participants. Surveys included questions on demographic and socio-economic factors, and fuels used in the home currently and during childhood, and their proximity to heating and cooking sources. Results When accounting for confounding demographic factors, odds ratios (OR) derived from binomial regression illustrates a significantly increased risk of esophageal cancer among those who use firewood as their primary cooking fuel (OR: 2.187; CI: 1.368-3.557). Women were almost three times as likely to have esophageal cancer when using firewood as the primary cooking fuel (OR: 2.821; CI: 1.255-6.917). Risk of esophageal cancer was significantly greater among participants who cooked in their living room (OR: 1.954; CI: 1.234-3.107). Findings demonstrate greater wood burning exposure is associated with significantly heightened risk of esophageal cancer. Conclusions Findings from the ESCCAPE case-control study indicate the potential role of exposure to smoke from firewood used in cooking and heating, in the complex aetiology of ESCC. Given the increased lifetime exposure to woodsmoke for women due to traditional domestic roles, and their lower exposure to other known risk factors, reliance on solid fuels for domestic energy could be an important potentially preventable risk factor for women in areas when the occurrence of ESCC is high.

Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study in China.

Simple SummaryChina accounts for half of the global new cases of esophageal cancer (EC). A disorder of individual trace elements was established as increasing risk for developing esophageal cancer, but the truth was that people are exposed to multiple metals simultaneously in the real world, and research on the relationship between mixtures of accumulative hazards and EC remains scarce. In our current research, we used BKMR, an approach designed to estimate the overall effect of a mixture, to explore the possible role of different trace elements combined in esophageal squamous cell carcinoma (ESCC) risk. In addition, some interesting results were found in our study. We hope it will provide more evidence for environment-related carcinogenesis of ESCC.We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was established to explore the associations and the cumulative and mixed effects of multiple trace elements on ESCC. Three elements (Zn, Se and Sr) displayed a negative trend with risk for ESCC, and a significant overall effect of the mixture of Al, V, Mn, Ni, Zn, Se and Sr on ESCC was found, with the effects of V, Ni and Sr being nonlinear. Bivariate exposure–response interactions among these trace elements indicated a synergistic effect between Zn and Se, and an impactful difference of V combined with Ni, Sr or Zn. Our results indicate that Ni, V, Al, Mn, Zn, Se and Sr are associated with ESCC risk, providing additional evidence of the complex effects of trace elements disorder during the etiology of EC development.

A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case–control studies

BackgroundConsumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score.MethodsFrom the ESCCAPE case–control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge.ResultsThe study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for ‘very hot’ vs ‘hot’), waiting time before drinking/eating (1.76 (1.37, 2.26) for <2 vs 2–5 minutes), consumption speed (2.23 (1.78, 2.79) for ‘normal’ vs ‘slow’) and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3.ConclusionsThermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.

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.

Tobacco and other risk factors for esophageal squamous cell carcinoma in Lilongwe Malawi: Results from the Lilongwe esophageal cancer case: Control study.

Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4-4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8-9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3-6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1-2.5 p = 0.021). Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted.

The Influence of Socioeconomic Status on Esophageal Cancer in Taiwan: A Population-Based Study.

Background: Esophageal cancer has extreme worldwide demographic and histologic variations in occurrence; thus, understanding the pathogenesis of esophageal cancer must be region- or country-based. We examined the incidence and tumor stage at diagnosis of esophageal cancer in relation to patients’ socioeconomic status (SES) in Taiwan. Method: This retrospective cohort study used data from Taiwan’s National Health Insurance Research Database and Taiwan Cancer Registry collected between January 2008 and December 2014. The records of 40- to 79-year-old patients diagnosed with esophageal cancer were retrieved. The distribution of the crude incidence rates of esophageal cancer by occupation and income variables was studied retrospectively. Cox proportional hazard model was used to adjust for potential confounders and compare the esophageal cancer incidence among four independent variables: age, gender, occupation, and income. Logistic regression analysis was applied to find the power of the independent variables on the odds ratio of late-stage presentation. Results: The analysis included 7763 subjects. Esophageal squamous cell carcinoma (ESCC) was the predominant histological type (96.6%) and 94.4% of patients were male. The peak affected age for ESCC was 50 to 59 years, whereas the risk of esophageal adenocarcinoma increased progressively with age. The risk of ESCC was significantly unfavorable for the most disadvantaged group, either in occupation or income, while in EAC, risk was unrelated to either factor. The stage of cancer at diagnosis was lower in the highest income groups than in the other two groups. Conclusion: Significant SES disparities in esophageal cancer incidence, based on occupation and income, are present in Taiwan. Low SES populations have a higher percentage of late-stage diagnosis. Resolution of the increasing socioeconomic disparities and narrowing the gaps in health inequities in Taiwan are needed.

Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study.

Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115-bp MethyLight assay. Categorical data were compared by the Chi-square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high-grade ESCdys (high-grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000-bootstrap resample. A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p=0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p=0.225). Bootstrap validation showed optimism-corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma

BackgroundThe relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk.MethodsThis case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model.ResultsWhen comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21–0.51), PUFA (OR: 0.32, 95% CI: 0.20–0.51), and TFA (OR: 0.44, 95% CI: 0.28–0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19–0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC.ConclusionsThis study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma.

Cadmium (Cd) exposure has been implicated in the etiology of esophageal squamous cell carcinoma (ESCC), albeit with inconsistent results from epidemiologic studies and without causal evidence. In this study, we explore the relationship of Cd exposure and the development, progression and therapeutic resistance of ESCC. A total of 150 ESCC patients and 177 matched controls from a coastal region with a high incidence of ESCC in China were included in the study. It was found that the median blood Cd level (BCL) was significantly higher in ESCC patients than that in the controls. Odds ratios for ESCC risk were 3.12 (95% CI 1.54-6.30) and 3.71 (95% CI 1.84-7.48) in the third and fourth quartiles of Cd distribution, respectively. Notably, BCL above 4.71 μg/L was strongly associated with shorter progression-free survival time compared to that below 1.60 μg/L (p < 0.001). The chronic Cd-treated ESCC cells (CCT-ESCC) CCT-EC109 and CCT-EC9706 exhibited increased cell proliferation and tumorigenesis, enhanced migration and invasion, and upregulated EMT biomarkers following 12 weeks of exposure to 5 μM cadmium chloride. Furthermore, Cd treatment attenuated the efficacy of 5-fluorouracil, cisplatin and irradiation treatment in CCT-ESCC cells both in vitro and in vivo. Moreover, we revealed that Cd stimulated the cancer cell stemness and Wnt/β-catenin signaling pathway in the CCT-ESCC cells. Additionally, 5-aza-2-deoxy-cytidine treatment resulted in suppression of the Wnt/β-catenin signaling pathway and rescue of the Cd-induced cell radioresistance. These results offer new insights into the role of environmental Cd exposure in the development, progression and chemoradioresistance of ESCC.

Risk Factors Associated With Early-Onset Esophageal Cancer in Tanzania.

PURPOSEEastern Africa is one of several regions affected by high incidence rates of esophageal squamous cell carcinoma (ESCC). A unique epidemiologic feature of ESCC in Eastern Africa is the high incidence in young people, with one-third of cases diagnosed at age < 45 years. This study aimed to investigate risk factors for early-onset ESCC in Tanzania through a secondary analysis of a matched case-control study.MATERIALS AND METHODSFrom 2013 to 2015, ESCC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Hospital controls were identified from patients with nonmalignant conditions and matched 1:1 for sex and age (± 10 years). Questionnaires were used to assess sociodemographic characteristics and environmental, dietary, and lifestyle risk exposures. Multivariate logistic regression models were used to estimate age-specific odds ratios of ESCC for exposures among participants age 30-44 and ≥ 45 years.RESULTSA total of 471 cases and 471 controls were enrolled. Among cases, 100 (21%) were < 45 years. Multiple exposures were identified as risk factors for early-onset ESCC, several of which were unique to this age group, including infrequent teeth cleaning, secondhand tobacco smoke exposure, and pest infestation of grain and/or nuts. Lower socioeconomic status, family history of ESCC, tobacco smoking, home-brewed alcohol consumption, home storage of grain and/or nuts, and use of firewood for cooking were associated in the older but not the younger age group. Hot beverage intake was associated with increased ESCC risk in both age groups.CONCLUSIONOur results suggest that ESCC risk factors in Tanzania vary between age groups. With the data currently available, environmental and behavioral risk factors appear to play an important role in the high incidence of ESCC among young people.

MDM4 polymorphisms associated with the risk but not the prognosis of esophageal cancer in Cixian high-incidence region from northern China.

The mouse double minute 4 (MDM4) may contribute to tumorgenesis by inhibiting p53 tumor suppressor activity. This study was designed to investigate whether MDM4 polymorphisms could affect susceptibility to esophageal squamous cell carcinoma (ESCC) and the survival of ESCC patients in a population from Cixian high-incidence region of northern China, which has not been explored. MDM4 rs1380576 and rs4245739 were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) in 568 ESCC patients and 578 controls. Compared to rs1380576 C/C genotype, C/G genotype was associated with decreased risk of ESCC (odds ratio [OR]=0.761, 95% confidence interval [CI]=0.595-0.973). Compared to rs4245739 A/A genotype, A/C or C/C genotype was related to increased susceptibility to ESCC (OR=1.551, 95% CI=1.001-2.402). Individuals with GC haplotype had significantly higher risk of ESCC than those with CA or GA haplotype (OR=1.598, 95% CI=1.048-2.438). Neither rs1380576 nor rs4245739 influenced the survival of ESCC patients. rs1380576 and rs4245739 may be used to predict susceptibility to ESCC for population in Cixian high-incidence region.

Dietary patterns and severity of symptom with the risk of esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional latent class analysis

BackgroundDietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease.MethodsWe analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40–69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram.ResultsWe identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: “Healthy”, “Western”, “Lower consumers-combination”, “Medium consumers-combination” and “Higher consumers-combination” patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into “Asymptomatic”, “Mild symptoms” and “Overt symptoms” classes based on health-related symptoms reported by the participants. Compared to the “Healthy” pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the “Asymptomatic”. The nomograms reflect the good predictive ability of the model.ConclusionAmong individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

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.

Alcohol consumption as a risk factor for oesophageal squamous cell carcinoma risk in sub-Saharan Africa

Epidemiological studies from many parts of the world have reported alcohol consumption as a risk factor for oesophageal squamous cell carcinoma (ESCC) and that this relationship is dose-dependent,1 but evidence from Africa has been inconsistent.2 In sub-Saharan Africa, the burden of ESCC is substantially higher in the eastern regions than western regions,3 but reasons for this difference are yet to be established. There is evidence that the total adult consumption of alcohol per capita is higher in western Africa than eastern Africa, suggesting that alcohol consumption on its own is unlikely to be driving these observed differences in disease burden.

Tumor-associated autoantibodies in ESCC screening: Detecting prevalent early-stage malignancy or predicting future cancer risk?

Background: To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk.Methods: Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models.Findings: In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P<0·0001; male: AUCfull model=0·662, 95% CI=0·596-0·728, AUCquestionnaire-based model=0·619, 95% CI=0·548-0·690, NRI=0·357, P=0·0028). This improvement was also seen in validation set, but was not similarly effective in distinguishing long-term incident cases from healthy controls.Interpretation: Serological autoantibodies against NY-ESO-1, STIP1, and MMP-7 perform well in detecting early-stage esophageal malignancy, but are less effective in predicting future ESCC risks.Funding: This work was supported by the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the National Key R&D Program of China (2016YFC0901404), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204), and the Natural Science Foundation of Beijing Municipality (7182033).

Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma

Purpose The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. Methods The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case–control studies, each of which included a population-based set and a hospital-based set. Results The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (p < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23–2.60 and 1.10–4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (p > 0.05). Conclusions The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.