Incidence Of Esophageal Squamous Cell Carcinoma Research Articles

Alcohol Intake Interacts with Functional Genetic Polymorphisms of Aldehyde Dehydrogenase (ALDH2) and Alcohol Dehydrogenase (ADH) to Increase Esophageal Squamous Cell Cancer Risk

IntroductionStudies have reported alcohol consumption and genetic variants as major contributing factors for esophageal squamous cell carcinoma (ESCC). However, the complicated interactions between alcohol and genetic factors involved in alcohol metabolism have not been well elucidated with respect to augmented risk of ESCC. MethodsWe performed a large population-based case-control study in a Chinese city with a high ESCC incidence by enrolling 1190 case patients and 1883 controls. We integrated candidate single-nucleotide polymorphism data, detailed alcohol consumption records, gene-alcohol interactions, and single-nucleotide polymorphism functional information to untangle the complicated relationship between alcohol, variants of genes encoding alcohol metabolism enzymes, and ESCC risk. The gene-alcohol interaction was tested by including their product term in a multivariable logistic regression model. Synergy index and ratio of ORs were calculated to assess interaction on additive and multiplicative scale, respectively. ResultsWe confirmed two ESCC susceptibility loci, rs671 in aldehyde dehydrogenase 2 family member gene (ALDH2) and rs1042026 in alcohol dehydrogenase 1B (class I), beta polypeptide gene (ADH1B), that significantly altered alcohol consumption behavior and subsequently modified the association between alcohol consumption and ESCC risk. The rs671(A) allele was associated with ESCC risk in alcohol drinkers (adjusted odds ratio =1.98, 95% confidence interval [CI]: 1.51–2.60) but not in nondrinkers. Healthy individuals who carry different ALDH2 and ADH1B genotypes exhibit diversified drinking behavior, with the proportion of drinkers varying between 23.7% and 54.3%. Among individuals with a fast ethanol oxidization rate, we observed a strong interaction between heavy alcohol consumption and ethanal oxidization rate on both the additive scale (synergy index 4.80 [95% CI: 1.82–12.68]) and the multiplicative scale (ratio of ORs 2.93, 95% CI: 1.39–6.35). ConclusionsOur observation highlights the need for preventing excessive use of alcohol, especially in individuals harboring active alcohol dehyrogenase and inactive ALDH2 variants.

Efficacy of endoscopic treatment on patients with severe dysplasia/carcinoma in situ of esophageal squamous cell carcinoma: A prospective cohort study.

ObjectiveTo explore the natural history of severe dysplasia/carcinoma in situ (SD/CIS) patients and to evaluate the efficacy of endoscopic treatment to SD/CIS patients. MethodsBetween January 2005 and December 2009, a population-based prospective screening program on esophageal squamous cell carcinoma (ESCC) was performed in Linzhou, China, with endoscopic screening plus iodine staining. All the eligible histologically confirmed SD/CIS patients were followed up through the door-to-door follow-up and local cancer registry. The endpoint was diagnosed as ESCC or the December 31st, 2016. Kaplan-Meier survival analysis and Log-rank test were used to compare the survival rates among treated and untreated patients.ResultsA total of 175 SD/CIS patients were enrolled and grouped by whether they received endoscopic treatment. Eleven-year cumulative incidence rates for untreated and treated SD/CIS patients were 10.7% [95% confidence interval (95% CI): 6.9−16.1] and 3.2% (95% CI: 1.4−7.0), respectively. The ESCC incidence free survival rate, and all-cause incidence and mortality free survival rates were all significantly higher in the treated patientsvs. untreated patients (P=0.043, P=0.008 and P=0.015, respectively). The ESCC mortality free survival rate showed no significant differences between the two groups (P=0.847). ConclusionsThe cumulative incidence rate of SD/CIS patients to ESCC was much lower than previously reported. The Kaplan-Meier survival analysis showed that endoscopic treatment could increase the ESCC and all-cause disease-free survival rates of SD/CIS patients significantly.

Metformin suppresses the esophageal carcinogenesis in rats treated with NMBzA through inhibiting AMPK/mTOR signaling pathway.

Metformin is a widely used antidiabetic drug for the management of type 2 diabetes mellitus. Recently, epidemiological studies demonstrate that metformin has anticancer effects on esophageal squamous cell carcinoma (ESCC) and other cancers. However, the effects and potential mechanisms of metformin on ESCC remain elusive. In this study, we used N-nitroso-N-methylbenzylamine (NMBzA), a special carcinogen for esophagi, to develop a rat ESCC model, in which the carcinogenesis progression of ESCC in rat was induced and promoted. We investigated the effects of metformin on carcinogenesis of ESCC in this model. Our results revealed that metformin significantly decreased the incidence and precancerous lesions of ESCC and inhibited proliferation and promoted apoptosis of esophageal epithelial cells in rat treated with NMBzA. Moreover, metformin also increased apoptosis and inhibited migration, colony formation and tumor sphere formation of human ESCC cells in vitro. Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6). Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro. Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC.

The role of definitive chemoradiotherapy versus surgery as initial treatments for potentially resectable esophageal carcinoma

BackgroundWe performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer.MethodsTo assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC).ResultsThe 2-year (OR = 1.199, 95% CI 0.922–1.560; P = 0.177) and 5-year overall survival (OS) rates (OR = 0.947, 95% CI 0.628–1.429; P = 0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR = 1.397, 95% CI 0.740–2.638; P = 0.303) or stage II–III (OR = 0.418, 95% CI 0.022–7.833; P = 0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR = 0.226, 95% CI 0.044–1.169; P = 0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR = 1.522, 95% CI 1.035–2.238; P = 0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR = 1.06, 95% CI 0.79–1.42; P = 0.70).ConclusionsdCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.

Age at Initiation and Frequency of Screening to Prevent Esophageal Squamous Cell Carcinoma: An Economic Evaluation in High Risk Regions

Background: Esophageal squamous cell carcinoma (ESCC) contributed substantial disease burden. The aim of this study was to identify the economic screening strategies for ESCC in high risk regions. Methods: For this economic evaluation, we developed and validated an ESCC health policy model, which was used for comparing different screening strategies for ESCC. Strategies varied in terms of age at initiation and frequency of screening. Model inputs were mainly derived from parameter calibration, published literature and databases. We estimated the effects of each strategy on the incidence of ESCC in addition to costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratios (ICERs) , expressed as cost per QALY gained. Results: Compared with no screening, all competing screening strategies decreased the incidence of ESCC from 0.44% to 77.32% per 100,000 population, and augmented the number of QALYs (0.01-0.09 QALYs) over a lifetime horizon. Only one screening strategy had costs per QALY of over than US$1,151, and 30 strategies were shown as cost-saving. The cost-effective frontier were made up of ten screening strategies, included the strategies initiating at 35 - 40 years of age and repeated every 1-3 years, which gained over 90% of probabilities that was preferred in probabilistic sensitivity analysis at a $1,151/QALY willingness-to-pay threshold. Results were sensitive to the parameters related to the risks of developing basal cell hyperplasia/mild dysplasia. Conclusion: Endoscopy screening initiating at 35-40 years of age and repeated every 1-3 years could substantially reduce the disease burden and is cost-effective for general population in high-risk regions. Funding: This work was supported by an unrestricted grant from Shanghai Municipal Health Commission (No. 15GWZK0901, 2016ZB0304 and 2016-40044-002). The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. Conflict of interest: None of the authors have anything to declare. Ethics approval: This economic analysis was based on a literature review and modeling techniques; this study did not require approval from an Institutional Research Ethics Board.

Incidence Trends of Esophageal and Gastric Cancer Subtypes by Race, Ethnicity, and Age in the United States, 1997–2014

There is limited information on contemporary incidence rates and trends, by race, ethnicity, and age, for major subtypes of esophageal and gastric cancer in the United States. We examined the most recent nationwide incidence data for esophageal squamous cell carcinoma, esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) by race, ethnicity, and age in the United States. Average contemporary incidence rates (2010-2014) and annual percent changes in rates (from1997 through 2014) by race, ethnicity, and age were calculated for each cancer subtype using nationwide data compiled by the North American Association of Central Cancer Registries. From 1997 through 2014, overall esophageal squamous cell carcinoma incidence rates continuously decreased in both sexes and all racial and ethnic groups, although rates remained stable among younger non-Hispanic white women. Overall, EAC incidence rates decreased or stabilized during the most recent time period (2006-2007 through 2014) in men and women, after increasing from 1997 through 2006 and 2007. However, EAC incidence rates continued to increase from 1997 through 2014 in several subpopulations, including non-Hispanic white men younger than 50 years, non-Hispanic white women younger than 70 years, and Asian/Pacific Islander men (all ages combined). Overall GCA incidence rates increased among non-Hispanic whites, but decreased among Hispanics (men only) and Asian/Pacific Islanders. Although overall GNCA rates decreased in both sexes and all racial and ethnic groups, rates increased in younger age groups among men (all races and ethnicities combined) and non-Hispanic white, non-Hispanic black, and Hispanic women. Using high-quality nationwide population-based data, we found increasing incidence trends for EAC, GCA, and GNCA in several subpopulations in the United States.

Global time trends in the incidence of esophageal squamous cell carcinoma.

Background and aimsEsophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer worldwide (90%). We aimed to provide an update of the global temporal trends in the incidence of ESCC.MethodsIncidence data for ESCC were collected from 30 well-established cancer registries from 20 countries in Europe, Northern America, Australia, or Asia for 1970–2015. Time trends in annual age-standardized incidence rates of ESCC were assessed using joinpoint analysis and log-linear regression. Age–period–cohort analysis was used to estimate the influence of age, calendar-period, and birth-cohort on the observed time trends in incidence.ResultsThe age-standardized incidence rates of ESCC varied more than eightfold in men and sevenfold in women across populations. In 2012, the highest rate of ESCC in men was observed in Nagasaki, Japan (9.7/100,000 person-years) and in women in Scotland (2.7/100,000 person-years). In men, the incidence decreased globally during the study period, as well as during the last few years. In women, the incidence increased in Japan (three regions), the Netherlands, New Zealand, Norway, and Switzerland, whereas it stabilized or decreased in other populations. Among ethnic groups in the United States, black men and women had more pronounced decreases in incidence than other groups. Generally, birth-cohort effects were stronger determinants of incidence trends than calendar-period effects.ConclusionIn men, the global ESCC incidence has decreased over time. In women, the incidence trends vary across populations, and the rates have increased in some countries. Changes in the prevalence of tobacco smoking and alcohol consumption may have contributed to these time trends.

Dek overexpression in murine epithelia increases overt esophageal squamous cell carcinoma incidence.

Esophageal cancer occurs as either squamous cell carcinoma (ESCC) or adenocarcinoma. ESCCs comprise almost 90% of cases worldwide, and recur with a less than 15% five-year survival rate despite available treatments. The identification of new ESCC drivers and therapeutic targets is critical for improving outcomes. Here we report that expression of the human DEK oncogene is strongly upregulated in esophageal SCC based on data in the cancer genome atlas (TCGA). DEK is a chromatin-associated protein with important roles in several nuclear processes including gene transcription, epigenetics, and DNA repair. Our previous data have utilized a murine knockout model to demonstrate that Dek expression is required for oral and esophageal SCC growth. Also, DEK overexpression in human keratinocytes, the cell of origin for SCC, was sufficient to cause hyperplasia in 3D organotypic raft cultures that mimic human skin, thus linking high DEK expression in keratinocytes to oncogenic phenotypes. However, the role of DEK over-expression in ESCC development remains unknown in human cells or genetic mouse models. To define the consequences of Dek overexpression in vivo, we generated and validated a tetracycline responsive Dek transgenic mouse model referred to as Bi-L-Dek. Dek overexpression was induced in the basal keratinocytes of stratified squamous epithelium by crossing Bi-L-Dek mice to keratin 5 tetracycline transactivator (K5-tTA) mice. Conditional transgene expression was validated in the resulting Bi-L-Dek_K5-tTA mice and was suppressed with doxycycline treatment in the tetracycline-off system. The mice were subjected to an established HNSCC and esophageal carcinogenesis protocol using the chemical carcinogen 4-nitroquinoline 1-oxide (4NQO). Dek overexpression stimulated gross esophageal tumor development, when compared to doxycycline treated control mice. Furthermore, high Dek expression caused a trend toward esophageal hyperplasia in 4NQO treated mice. Taken together, these data demonstrate that Dek overexpression in the cell of origin for SCC is sufficient to promote esophageal SCC development in vivo.

Esophageal cancer male to female incidence ratios in Africa: A systematic review and meta-analysis of geographic, time and age trends

Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC’s Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30–39 year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomised controlled trial

ObjectiveDescription of the design and preliminary results of baseline recruitment and screening in the endoscopic screening for esophageal cancer in China (ESECC), the first randomised controlled trial (RCT) assessing efficacy...

A systematic literature review of studies reporting human papillomavirus (HPV) prevalence in esophageal carcinoma over 36 years (1982–2017)

A total of 203 reports published between 1982 and 2017 on the association between human papillomaviruses (HPV) and esophageal squamous cell carcinoma (ESCC), originating from 187 studies performed in 32 countries from six continents, were selected and reviewed. The selected studies included a total of 14,788 ESCC cases; the presence of HPV infection was detected in 30.9% of cases (95% CI 30.1-31.6%) and was the highest in regions with the highest incidence of ESCC. Across studies published in the last 6 years, Alphapapillomavirus species were detected in 31.1% of ESCCs (1,464/4,708, 95% CI 29.8-32.4%), of which 73.8% (1,080/1,464, 95% CI 71.5-76.0%) were positive for the presence of HPV16/18. HPV16 was by far the most common HPV type detected, accounting for 21.0% (799.5/3,803, 95% CI 19.8-22.4%) of the total number of ESCC cases investigated. Our results are in line with previously published studies, suggesting the etiological role of HPV in the development of a subset of ESCC cases. Although the association between HPV and esophageal adenocarcinoma (EAC) has been studied to a far lesser extent, some studies also suggest a potential etiological role of HPV in a subset of EAC cases.

Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya

BackgroundLow serum selenium status has been associated with increased risk of esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC incidence and is known to have low soil selenium levels, but this association has not previously been evaluated. In this study we assessed the association of serum selenium concentration and the prevalence of esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet, Kenya.Methods294 asymptomatic adult residents of Bomet, Kenya completed questionnaires and underwent endoscopy with Lugol’s iodine staining and biopsy for detection of ESD. Serum selenium concentrations were measured by instrumental neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI) for associations between serum selenium and ESD were calculated using unconditional logistic regression.ResultsThe mean serum selenium concentration was 85.5 (±28.3) μg/L. Forty-two ESD cases were identified (14% of those screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%) in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05–8.74) and this association remained after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06–14.19).ConclusionThis is the first study to evaluate the association of serum selenium concentration and esophageal squamous dysplasia in an African population at high risk for ESCC. We found a positive association between higher serum selenium concentration and prevalence of ESD, an association contrary to our original hypothesis. Further work is needed to better understand the role of selenium in the etiology of ESCC in this region, and to develop effective ESCC prevention and control strategies.

Expression of P-EGFR and P-Akt protein in esophageal squamous cell carcinoma and its prognosis.

The phosphorylated epidermal growth factor receptor (P-EGFR) and phosphorylated Akt (P-Akt) protein in esophageal squamous cell carcinoma (ESCC) were studied, and its significance in clinical prognosis of patients was assessed. The expression of P-EGFR and P-Akt protein in 83 cases of ESCC and 83 normal esophageal tissues was determined by immunohistochemical staining. Log-rank test and correlation analysis were used to analyze the prognosis of ESCC. The positive expression of P-EGFR in ESCC was 88% (73/83 cases) compared with 41% in normal esophageal mucosa (34/83 cases) (P<0.05). The rate of P-Akt protein expression in ESCC was 90.4% (75/83 cases), compared with 27.7% seen in normal esophageal mucosa (23/83 cases) (P<0.05). The expression of P-EGFR and P-Akt protein was positively correlated with lymph node metastasis and degree of differentiation (P<0.05) irrespective of sex, age, tumor diameter and TNM stage (P>0.05). The expression of P-EGFR was positively correlated with that of P-Akt protein (r=0.674, P<0.01). P-EGFR expression was negatively correlated with survival time of patients with ESCC (r=−0.526, P<0.01). The Kaplan-Meier survival curves showed that the cumulative survival rate of P-EGFR-positive cases was significantly lower than that of the P-EGFR-negative cases (P<0.01). The expression of P-Akt was negatively correlated with survival in patients with ESCC (r=−0.473, P<0.01). The Kaplan-Meier survival curves showed that the cumulative survival rate of the P-Akt-positive cases was significantly lower than that of the P-Akt-negative cases (P<0.01). In conclusion, P-EGFR and P-Akt protein expression is closely related to the incidence of ESCC and mediates the development of invasive cancer and metastasis. It is used to determine the prognosis of ESCC, and may represent a new therapeutic target for the disease.

Abstract 5566: African American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks

Abstract Background: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), this subtype that shows a marked variation in geographic incidence. So far, the molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate of these patients worse than those of other ethnic groups. Our aim is to investigate the central question of whether there is a genetic basis for the aggressive nature of ESCC among African-Americans through analysis of genetic overlaps and differences between African-American ESCC and reported Asian data. Methods: We conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched controls to define genetic alterations that occur in African American ESCC. We then utilized Ingenuity Pathway Analysis (IPA) to analyze the differentially expressed genes in African-American ESCC. We conducted a meta-analysis of differentially expressed genes of African American ESCC and those of Asian ESCC through IPA. Results: Transcriptome profiling of African- American ESCC tumors versus adjacent normal esophageal tissues revealed significant differential expression of 756 genes. Among the most strongly up-regulated genes were keratin 17, immunoglobulin genes and ornithine decarboxylase 1. Genes that showed a great loss of expression included cysteine-rich secretory protein 3 and sciellin. We performed pathway and network analysis on significantly dysregulated genes using IPA to determine the overall biological impact of the widespread transcriptional aberration in African-American ESCC. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in carcinogenesis in ESCC in African Americans. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. A meta-analysis of ESCC expression profiles in our African American sample and those of several Asian samples determined genes in the NRF2 pathway are uniquely and significantly altered in African-American ESCC. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular property of African-American ESCC a widespread and prominent involvement of NRF2 pathway. Conclusion: Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC. Citation Format: Hayriye Verda Erkizan, Jack Lichy, Vincente Notario, Robert Wadleigh. African American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2017-5566

Racial and Ethnic Disparities in the Incidence of Esophageal Cancer in the United States, 1992-2013.

Racial and ethnic disparities in the incidence of esophageal cancer have not been thoroughly characterized with quantitative health-disparity measures. Using data from 1992-2013 from 13 US cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities according to histological type, based on a variety of disparity metrics. The age-standardized incidence rate of squamous cell carcinoma (SCC) was highest among black persons, while adenocarcinoma mainly affected white men. The rate of SCC decreased over time in all racial/ethnic groups, and this was most pronounced in black persons (by 5.7% per year among men and 5.0% among women). The adenocarcinoma rate rose among non-Hispanic whites and among black men. Racial/ethnic disparities in the incidence of total esophageal cancer decreased over time, which was due mainly to reduced disparities in SCC. The 2 absolute disparity measures-range difference and between-group variance-for adenocarcinoma rose by 3.2% and 6.8% per year, respectively, in men and by 1.8% and 5.3% per year, respectively, in women. This study demonstrates decreased racial/ethnic disparities in the incidence of esophageal SCC over time in the United States, while disparities increased in adenocarcinoma incidence as measured on the absolute scale.

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks

BackgroundEsophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups.MethodsTo begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues.ResultsWe found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway.ConclusionTaken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

Predicting the Future Burden of Esophageal Cancer by Histological Subtype: International Trends in Incidence up to 2030.

Rapid increases in the incidence of esophageal adenocarcinoma (EAC) in high-income countries in the past decades have raised public health concerns. This study is the first to predict the future burden of esophageal cancer by histological subtype using international incidence data. Data on esophageal cancer incidence by year of diagnosis, sex, histology, and age group were extracted from 42 registries in 12 countries included in the last three volumes (VIII-X) of Cancer Incidence in Five Continents, contributing at least 15 years of consecutive data. Numbers of new cases and incidence rates were predicted up to 2030 by fitting and extrapolating age-period-cohort models; the differential impact of demographic vs. risk changes on future cases were examined. The number of new AC cases is expected to increase rapidly 2005-2030 in all studied countries as a combined result of increasing risk and changing demographics. In contrast, the incidence of esophageal squamous cell carcinoma (ESCC) is predicted to continue decreasing in most countries. By 2030, 1 in 100 men in the Netherlands and the United Kingdom are predicted to be diagnosed with EAC during their lifetime. The burden from EAC is expected to rise dramatically across high-income countries and has already or will surpass ESCC incidence in the coming years, especially among men. Notwithstanding the inherent uncertainties in trend-based predictions and in subtype misclassification, these findings highlight an ongoing transition in the epidemiology of esophageal cancer that is highly relevant to future cancer control planning and clinical practice.

Alcohol abstinence and risk assessment for second esophageal cancer in Japanese men after mucosectomy for early esophageal cancer.

BackgroundAlcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2.MethodsProspective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676).ResultsSixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12–3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14–0.97]).ConclusionsBoth the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC.

The Race-Specific Incidence of Esophageal Squamous Cell Carcinoma in Individuals With Exposure to Tobacco and Alcohol.

The relative impact of esophageal squamous cell carcinoma (ESCC) in minority populations is incompletely understood. We aimed to estimate the race-specific incidences of ESCC and place these in the context of the incidence of esophageal adenocarcinoma (EAC) in white men with gastroesophageal reflux disease (GERD). The race- and sex-specific exposures to tobacco and alcohol in the United States were obtained from the National Health Interview Survey. The standardized incidence ratios of exposure to tobacco smoke and/or alcohol for ESCC were estimated from meta-analyses. Existing incidences of ESCC in the United States were obtained from the Surveillance, Epidemiology, and End Results (SEER) program. We then used this data to inform a Markov computer model estimating the incidence of ESCC. The incidence of ESCC reported in SEER was the greatest among African-Americans compared with white non-Hispanics, Hispanics, or Asians. In our model, the estimated incidence of ESCC in African-American men exposed to tobacco and alcohol approached the risk of EAC in white non-Hispanic men with weekly GERD. For instance, at age 60 years, the incidence of ESCC in African-American men who have used both tobacco and alcohol was 30/100,000 compared with an incidence of EAC in white men with GERD of 40/100,000. In comparison, the risk of EAC in white non-Hispanic women with weekly GERD at this age was 6.2/100,000. The incidence of ESCC in African-American men who use alcohol and tobacco is the highest and comparable to other screened diseases. Development of screening and prevention programs for ESCC in high-risk populations should be considered.