Assessment of LINC-PINT genetic polymorphisms and esophageal squamous cell carcinoma risk in the Hainan Han population.

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high incidence and mortality rates worldwide. This study aimed to investigate the correlation between LINC-PINT polymorphisms and ESCC risk in the Hainan Han population. METHODS: A total of 391 patients with ESCC and 452 healthy controls were enrolled to evaluate the effect of LINC-PINT SNPs (single nucleotide polymorphisms) on ESCC susceptibility. Associations were evaluated by calculating odds ratios (OR) and 95% confidence intervals (CIs). Multifactor dimensionality reduction analysis was performed to explore the association between SNP-SNP interactions and ESCC susceptibility. We further determined the correlation between clinical indicators and SNP in patients with ESCC. RESULTS: Our study showed that rs157916 (OR 0.63, p = 0.011) and rs157928 (OR 0.80, p = 0.021) were associated with a decreased risk of ESCC. Stratified analysis indicated that rs157916 could decrease the risk of ESCC in people aged >64 years, in males, and non-drinkers (OR 0.58, p = 0.042; OR 0.58, p = 0.010; OR 0.62, p = 0.025, respectively). Rs16873842 was related to a decreased risk of ESCC in males (OR 0.70, p = 0.015). Rs7801029 was associated with ESCC risk in females (OR 0.39, p = 0.033) and non-drinkers (OR 0.68, p = 0.040). Rs7781295 decreased the ESCC risk in smokers (OR 0.58, p = 0.046) and drinkers (OR 0.58, p = 0.046). In addition, rs157928 played a protective role in ESCC risk in females (OR 0.39, p = 0.033) and non-smokers (OR 0.32, p = 0.006). Additionally, the best predictive model for ESCC was a combination of rs157916, rs16873842, rs7801029, rs7781295, rs28662387, and rs157928. CONCLUSION: Our study revealed that LINC-PINT polymorphisms were associated with ESCC risk.

The Ethics of Cancer Screening Based on Race and Ethnicity.

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity.Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk.Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification.

The distribution of esophageal cancer patients enrolled in care at the Uganda Cancer Institute by sub-regions, districts and ethnicity.

Background: There is limited published data regarding the distribution of esophageal cancer patients by sub-regions, districts and ethnicity in Uganda. Objectives: To study the distribution by sub-regions, districts, ethnicity and sub-regions post-care outcomes of esophageal cancer patients in care over ten years at the Uganda Cancer Institute. Methods: Patients' charts with confirmed diagnoses of esophageal cancer for 2009-2019 were identified. Case information, which included demographics, clinical presentation, distribution by sub-regions, districts, ethnicity and sub-regions post-care outcomes, were retrospectively abstracted. Results: Central 671(34.15%), Southwestern 308(15.67%), Elgon 176(8.95%) and East central 163(8.29%) sub-regions had most patients. Mostly from administrative districts of Wakiso 167(8.50%), Mbarara 51(2.59%), Tororo 53(2.70%), Busia 33(1.68). Baganda, Banyakole, Bagisu and Basoga ethnic groups predominate. Patients from neighbouring countries were mainly from Rwanda 56(2.85%), South Sudan 24(1.22%), then Kenya 21(1.07%), and Rwandese, Dinka and Luo by ethnicity, respectively. Central and Southwestern sub-regions had the most post-care outcomes of the patients regarding living, death, and loss to follow-up. Conclusion: Patients are commonly from the administrative districts of Central, Southwestern, Elgon and East Central sub-regions and neighbouring countries of Rwanda, South Sudan and Kenya. Baganda, Banyakole, Bagisu and Basoga are the main ethnic groups. Central and Southwestern sub-regions are with most post-care outcomes.

Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers.

INTRODUCTION: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities. METHODS: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines. RESULTS: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95). DISCUSSION: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.

Esophageal cancer in Hispanics: a demographic analysis of the National Cancer Database.

BACKGROUND: Hispanics are the fastest-growing minority and the second largest ethnic group in the United States, accounting for 18% of the national population. The American Cancer Society estimated 18,440 new cases of esophageal cancer (EC) in the United States in 2020. Hispanics are reported to be at high risk of EC. We sought to interrogate the demographic patterns of EC in Hispanics. Secondary objective was to examine evidence of socioeconomic disparities and differential therapy. METHODS: We identified Hispanic vs non-Hispanic patients with EC in the National Cancer Database between 2005 and 2015. Groups were statistically equated through propensity score-matched analysis. RESULTS: A total of 3205 Hispanics (3.8%) were identified among 85,004 patients with EC. We identified significant disparities between Hispanic and non-Hispanic groups. Disparities among Hispanics included higher prevalence of squamous EC, higher likelihood of stage IV cancer diagnosis, younger age, uninsured status, and income< $38,000. Hispanics were less likely to have surgical intervention or any type of treatment when compared to non-Hispanics. Multivariate analysis showed that age, ethnicity, treatment, histology, grade, stage, and Charlson-Deyo scores were independent predictors of survival. Treated Hispanics survived longer than non-Hispanics. CONCLUSION: Despite the lower prevalence of EC, there is a disproportionately higher prevalence of metastatic and untreated cases among Hispanics. This disparity may be explained by Hispanics' limited access to medical care, exacerbated by their socioeconomic and insurance status. Further study is warranted to examine these health disparities among Hispanics.

Asian Americans have higher 30-day surgical complications after esophagectomy: A propensity-score matched study from ACS-NSQIP database.

BACKGROUND: Despite Asian Americans having a heightened risk profile for esophageal cancer, racial disparities within this group have not been investigated. This study seeks to evaluate the 30-day postoperative outcomes for Asian Americans following esophagectomy. METHODS: A retrospective analysis was performed using ACS-NSQIP esophagectomy targeted database 2016-2021. A 1:3 propensity-score matching was applied to Asian Americans and Caucasians who underwent esophagectomy to compare their 30-day outcomes. RESULTS: There were 229 Asian Americans and 5303 Caucasians identified. Asian Americans were more likely to have squamous cell carcinoma than adenocarcinoma. After matching, 687 Caucasians were included. Asian Americans had higher pulmonary complications (22.27 â€‹% vs 16.01 â€‹%, p â€‹= â€‹0.04) especially pneumonia (16.59 â€‹% vs 11.06 â€‹%, p â€‹= â€‹0.04), renal dysfunction (2.62 â€‹% vs 0.44 â€‹%, p â€‹= â€‹0.01) especially progressive renal insufficiency (1.31 â€‹% vs 0.15 â€‹%, p â€‹< â€‹0.05), and bleeding events (18.34 â€‹% vs 9.02 â€‹%, p â€‹< â€‹0.01). In addition, Asian Americans had longer LOS (11.83 â€‹± â€‹9.39 vs 10.23 â€‹± â€‹7.34 days, p â€‹= â€‹0.03). CONCLUSION: Asian Americans were found to face higher 30-day surgical complications following esophagectomy. Continued investigation into the underlying causes and potential mitigation strategies for these disparities are needed.

Evaluating the Impact of Race and Ethnicity on Health-Related Quality of Life Disparities in Patients with Esophageal Cancer: A SEER-MHOS National Database Study.

BACKGROUND: It is unclear whether health-related quality of life (HRQOL) disparities exist between racial/ethnic groups in older patients with esophageal cancer, pre- and post-diagnosis. METHODS: Using the SEER-MHOS (Surveillance, Epidemiology, and End Results and Medicare Health Outcomes Survey) national database, we included patients ages 65-years-old or greater with esophageal cancer diagnosed from 1996 to 2017. HRQOL data within 36 months before and after diagnosis were measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36 and VR-12 instruments. Total combined score (TCS) was reflected by both PCS and MCS. RESULTS: We identified 1,312 patients, with evaluable data on 873 patients pre-diagnosis and 439 post-diagnosis. On pre-diagnosis cohort MVA, the MCS was better for White over Hispanic patients (54.1 vs. 48.6, P = 0.012). On post-diagnosis cohort MVA, PCS was better for Hispanic compared with White (39.8 vs. 34.5, P = 0.036) patients, MCS was better for Asian compared with White (48.9 vs. 40.9, P = 0.034) patients, and TCS better for Asian compared with White (92.6 vs. 76.7, P = 0.003) patients. CONCLUSIONS: In older patients with esophageal cancer, White patients had better mental HRQOL as compared with Hispanic patients pre-diagnosis. However, post-diagnosis, White patients had worse mental and physical HRQOL compared with Asian and Hispanic patients, respectively, suggesting a greater negative impact on self-reported HRQOL in White patients with esophageal cancer. IMPACT: To our knowledge, this study is the first to explore HRQOL differences in patients with esophageal cancer of various racial and ethnic groups and warrants further validation in future studies.

The Dynamic Changing Incidence of Gastric Cancer in Israel: Time for a National Surgical Management Committee?

BACKGROUND: There has been a general reduction over the last 20 years in the incidence within Israel of gastric cancer (GC). This has particularly been noted in the Jewish population with a slight increase in the incidence of cancer of the gastroesophageal junction among Jews of Sephardi origin. Given the diversity of individual ethnic subpopulations, the effects of GC incidence in second-generation immigrant Jews, particularly from high prevalence regions (e.g., the former Soviet Union, Iraq, and Iran), awaits determination. There are currently no national data on GC-specific mortality. The most recent available cross-correlated Israeli National Cancer Registry (INCR) and International Association for Cancer Research (IARC) incidence data for GC of the body and antrum in Israel are presented. Some of the challenges associated with GC monitoring in the changing Israeli population are discussed. We propose the establishment of a national GC management committee designed to collect demographic and oncological data in operable cases with the aim of recording and improving GC-specific outcomes. We believe that there is value in the development of a national surgical planning program, which oversees training and accreditation in a dynamic environment that favors the wider use of neoadjuvant therapies, minimally invasive surgery and routine extended (D2) lymphadenectomy. These changes should be supported by assessable enhanced recovery programs.

The risk and prognostic factors for brain metastases in esophageal cancer patients: an analysis of the SEER database.

BACKGROUND: Brain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients. METHODS: Retrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan-Meier method. RESULTS: A total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5-7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases. CONCLUSIONS: Homogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases.

Clinical significance of YAP1 and TAZ in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is the eighth most frequent and sixth most fatal cancer worldwide. This study aimed to investigate the clinical characteristics and prognostic significance of yes related protein 1 (YAP1) and transcriptional co-activator with PDZ binding motif (TAZ) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 306 ESCC pathological specimens and adjacent tissues (as control; tissues from the esophageal mucosa >5 cm from the edge of the tumor) were collected between January, 2008 and December, 2018. Immunohistochemical staining was used to assess the expression of YAP1 and TAZ proteins in the ESCC and adjacent tissues, and their relationship with clinicopathological parameters was evaluated using SPSS 21.0 software. RESULTS: YAP1 and TAZ proteins were highly expressed in ESCC, and their expression was closely related to TNM stage and lymph node metastasis. Expression of YAP1 was associated with tumor size (P = .029), differentiation (P = .000), depth of invasion (P = .001), and TNM stage (P = .000). Expression of TAZ was associated with tumor size (P = .034), differentiation (P = .000), depth of invasion (P = .029), lymph node metastasis (P = .006), and ethnicity (P < .001). The expression of YAP1 protein was positively correlated with the expression of TAZ protein (r = 0.257, P < .05). YAP1 and TAZ expression (P = .039 and .000, respectively), tumor size (P = .041), and lymph node metastasis (P = .001) significantly affected the overall survival of patients with ESCC, and represent independent factors for overall survival. CONCLUSION: YAP1 and TAZ proteins are highly expressed in ESCC, and closely related to the clinical and pathological parameters such as the diameter of the tumor, degree of differentiation, and depth of invasion, indicating that YAP1 and TAZ may be involved in the development of ESCC. YAP1 and TAZ may be used as prognostic markers in ESCC.

Racial disparities in provider recommendation for esophagectomy for esophageal carcinoma.

BACKGROUND: Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma. METHODS: A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable-adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan-Meier curves and log-rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics. RESULTS: After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I-III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67-3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3- and 5-year overall survival rates compared to White patients (log-rank p < 0.0001). CONCLUSION: Black patients with clinical stage I-III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta ‑ analysis

Objective Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. Methods We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. Results Five eligible studies (four cohort studies and one case–control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60–1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39–0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). Conclusions Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified (AU)

Circulating miR-21 as a potential biomarker in human digestive system carcinoma: a systematic review and diagnostic meta-analysis.

Purpose: Gastrointestinal cancers (GICs) account for about a quarter of cancers. Lately, the circulating microRNAs as a non-invasive biomarker for identifying and monitoring diseases have been recognized. Several studies have examined the role of miR-21 in digestive system carcinoma. We conducted a meta-analysis to assess the diagnostic role of miR-21 in GICs.Methods: Seventeen studies involving 1700 individuals were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, SROC, and Q* index were calculated based on true-positive, true-negative, false-negative, and false-positive. Moreover, the subgroup analyses have been performed for miR-21 based on sample types (serum/plasma), normalized genes (U6, miR-16, and miR-39), and ethnicity.Results: The pooled sensitivity 0.722 (95% CI: 0.70-0.74), specificity 0.820 (95% CI: 0.801-0.838), PLR 4.375 (95% CI: 3.226-5.933), NLR 0.308 (95% CI: 0.239-0.398), DOR 16.06 (95% CI: 9.732-26.53) as well as AUC 0.86, and Q* index 0.79 represented the high-grade diagnostic precision of miR-21 in identifying GICs (ESCC, GC, CRC, HCC, and PC).Conclusion: This meta-analysis demonstrated that circulating miR-21 levels can be used to monitor the digestive system carcinomas. Therefore, miR-21 can be a useful biomarker of progression and fair diagnosis in GICs patients.

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta­analysis.

OBJECTIVE: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

A Shared Susceptibility Locus in the p53 Gene for both Gastric and Esophageal Cancers in a Northwestern Chinese Population.

Background: Upper gastrointestinal tract cancers are the leading causes of cancer-related deaths in Northwest China and they share many similarities in terms of histological type, risk factors, and genetic variants. We hypothesized that shared common single-nucleotide polymorphisms (SNPs) in the p53 pathway exist between patients with gastric and esophageal cancer (EC) patients. Materials and Methods: A case-control study to examine genetic variants in the p53 pathway was conducted with subjects from a high-incidence area for upper gastrointestinal cancers of China. Multiple logistic regression analyses were used to estimate the association of genotypes with gastric cancer and EC risks. Median survival was estimated by using the Kaplan-Meier method and compared by using the log-rank test. Results: Compared with the rs1042522 Pro allele, the rs1042522 Arg allele was associated with an increased risk of gastric cancer (1.810×) and an increased risk of EC (2.285×). The rs1042522 Arg allele carriers who also smoked or consumed alcohol had a further increased risk for gastric cancer odds ratios (ORsmoking = 2.422, ORdrinking = 5.152) and EC (ORsmoking = 5.310, ORdrinking = 8.359). No association was found between the rs1042522 genotypes and survival (p > 0.05). Conclusion: The p53 rs1042522 arg allele together with tobacco smoking and alcohol drinking, was associated with an increased risk, for gastric cancer and EC, but not the survival among northwestern Chinese patients. These associations warrant confirmatory studies.

Investigation of IL-4, IL-10, and HVEM polymorphisms with esophageal squamous cell carcinoma: a case-control study involving 1929 participants.

It is believed that an individual's hereditary factors may be involved in the development of esophageal cancer (EC). The present study recruited 721 esophageal squamous cell carcinoma (ESCC) cases and 1208 controls and explored the roles of single nucleotide polymorphisms (SNPs) in the interleukin-4 (IL-4), IL-10, and herpesvirus entry mediator (HVEM) genes in contributing to ESCC risk. IL-4, IL-10, and HVEM SNPs were analyzed by employing an SNPscan method. After adjustment for body mass index (BMI), smoking, drinking, age and gender, we identified that the rs2070874 T>C locus in IL-4 gene decreased the risk of ESCC (CC vs. TT: P=0.008; CC vs. TT/TC: P=0.010). After a stratified analysis, we suggested that the IL-4 rs2070874 T>C variants might be a protective factor for ESCC in male, ≥63 years old, never smoking, drinking and BMI < 24 kg/m2 subgroups. In addition, we identified that the rs2243263 G>C polymorphism in IL-4 gene was a risk factor for ESCC development in the BMI ≥ 24 kg/m2 subgroup (GC vs. GG: P=0.030 and GC/CC vs. GG: P=0.018). We identified an association of the IL-4 rs2070874 T>C SNP with the decreased susceptibility of ESCC in stage I/II subgroup. Finally, we found an association of the IL-10 rs1800872 T>G SNP with a worse differentiation (TG vs. TT: P=0.048 and GG/TG vs. TT: P=0.032). In conclusion, the findings indicate a potential importance of IL-4 rs2070874 T>C, IL-4 rs2243263 G>C and IL-10 rs1800872 T>G SNPs in the development of ESCC.

Racial and ethnic disparities in mortality from gastric and esophageal adenocarcinoma.

BACKGROUND: Racial/ethnic differences in mortality have not been well studied for either non-cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator. METHODS: We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age-adjusted incidence-based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis. RESULTS: The mortality rate in NCGC was two- to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non-Hispanic whites, and was significant across all age groups and stages of disease (P < .01). Mortality in CGC was higher in non-Hispanic whites than blacks and Asians/PI, particularly in individuals in the 50-64 year age group and those with stage IV disease. Mortality in EAC was two- to sixfold higher in non-Hispanic whites than all other groups across all age groups and stages of disease. From 2004 to 2016, mortality rates were stable across all racial/ethnic groups in NCGC and CGC, and in minority groups with EAC, but have been rising in non-Hispanic whites with EAC (APC 3.03, 95% CI 0.17-5.96). CONCLUSIONS: This is the largest study of incidence-based mortality in CGC and NCGC and demonstrates racial/ethnic differences in mortality between these subtypes. Mortality rates for NCGC are highest in minority groups, and have been stable in recent years despite declining incidence. Mortality rates for CGC are marginally higher in middle-aged non-Hispanic whites with advanced disease, though have remained stable. In contrast, mortality in EAC has been rising for non-Hispanic whites, in parallel to incidence. Further studies are needed to refine prevention strategies for high-risk individuals dying from these specific cancer subtypes.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Disparities in esophageal cancer: less treatment, less surgical resection, and poorer survival in disadvantaged patients.

The incidence of esophageal cancer has increased steadily in the last decades in the United States. The aim of this paper was to characterize disparities in esophageal cancer treatment in different racial and socioeconomic population groups and compare long-term survival among different treatment modalities. A retrospective analysis of the National Cancer Database was performed including adult patients (≥18 years old) with a diagnosis of resectable (stages I-III) esophageal cancer between 2004 and 2015. Multivariable logistic regression models were used to determine the odds of being offered no treatment at all and surgical treatment across race, primary insurance, travel distance, income, and education levels. Multivariable Cox proportional hazards models were used to compare 5-year survival rates across different treatment modalities. A total of 60,621 esophageal cancer patients were included. Black patients, uninsured patients, and patients living in areas with lower levels of education were more likely to be offered no treatment. Similarly, black race, female patients, nonprivately insured patients, and those living in areas with lower median residential income and lower education levels were associated with lower rates of surgery. Patients receiving surgical treatment, compared to both no treatment and definitive chemoradiation, had significant better long-term survival in stage I, II, and III esophageal cancer. In conclusion, underserved patients with esophageal cancer appear to have limited access to surgical care, and are, in fact, more likely to not be offered any treatment at all. Considering the survival benefits associated with surgical resection, greater public health efforts to reduce disparities in esophageal cancer are needed.