Esophageal and Gastric Cancer Incidence and Mortality Trends in Norway, 1993–2022: A Registry-Based Study

Angiotensin-Converting Enzyme Inhibitors and Risk of Esophageal and Gastric Cancer: A Nested Case-Control Study

Simple SummaryThe incidence of esophageal cancer overall has increased in the United States, driven by increasing rates of esophageal adenocarcinoma (EAC). However, whether rates of EAC are still rising is unclear. We examined trends in esophageal cancer overall and within important sub-groups of the population. We found that esophageal squamous cell carcinoma (ESCC) rates have been steadily declining, while EAC rates rose rapidly before stabilizing in 2000. The trend of decreasing incidence of ESCC was observed almost uniformly by age group, sex, and race/ethnicity, while trends in EAC rates varied across these sub-groups. A cohort effect for EAC was observed among people born during 1950, but EAC rates were stable across successive generations born between 1950 and 1985. Given the continued rising rates of known EAC risk factors, including obesity and gastroesophageal reflux disease, there is a need to continue monitoring trends for changes in incidence rates.Background: Esophageal cancer (EC) incidence rates overall have declined in recent decades; however, the two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), show divergent secular trends. Methods: Age-adjusted EC incidence rates were calculated using data from the Surveillance Epidemiology and End Results (SEER) 12 Program. We examined secular trends from 1992 to 2019 overall and by age group, sex, race/ethnicity, tumor location, and SEER registry. Joinpoint regression was used to compute annual percent changes (APC) and average annual percent changes (AAPC). We used age-period-cohort models to examine the potential impact of period and birth cohort effects on trends. Results: Between 1992 and 2019, overall EC incidence rates declined by 0.54% annually (95% confidence interval [CI]: −0.75%, −0.33%). While ESCC rates declined linearly throughout the study period (AAPC = −2.85; 95%CI: −3.05%, −2.65%), EAC rates increased by over 5% annually from 1992 to 2000 (APC = 5.17; 95%CI: 3.28%, 7.10%), before stabilizing from 2000 to 2019 (APC = 0.22; 95%CI: −0.16%, 0.60%). Trends in ESCC and EAC varied by age group, sex, and race/ethnicity. Relative to ESCC rates among cohorts born circa 1950, the rates were 81% lower in cohorts born circa 1985 (rate ratio, 0.19; 95%CI: 0.04, 0.96). For EAC, rates have remained stable across successive birth cohorts since 1950. Conclusions: We observed linear declines in EC rates overall and for ESCC across age, sex, and race/ethnicity subgroups, but an inconsistent pattern for EAC. The trends in EAC cohorts born after 1955 were stable and suggest that EAC rates may have peaked in the U.S.

This study describes recent trends in incidence, survival and prevalence of subgroups of esophageal and gastric cancer in Linzhou city between 2003 and 2009. Data of esophageal and gastric cancer for the period of interest were extracted from the Linzhou Cancer Registry. Using information on tumor morphology or anatomical site, data were divided into six groups; esophageal squamous cell carcinoma, esophageal adenocarcinoma, other and unspecified types of esophageal cancer, and cardia, non-cardia, and unspecified anatomical site of stomach cancer. Incidence, survival and prevalence rates for each of the six cancer groups were calculated. The majority of esophageal cancers were squamous cell carcinomas (82%). Cardiac cancer was the major gastric cancer group (64%). The incidence of esophageal squamous cell carcinoma and gastric cardiac cancer increased between 2003 and 2009. Both esophageal and gastric cancer had a higher incidence in males compared with females. Overall survival was poor in all sub-groups with 1 year survival ranging from 45.9 to 65.6% and 5 year survival ranging from 14.7 to 30.5%. Prevalence of esophageal squamous cell carcinoma and gastric cardiac cancer was high (accounting for 80% overall). An increased focus on prevention and early diagnosis, especially in esophageal squamous cell carcinoma and gastric cardiac cancer, is required.

Vegetarian Diets and Breast Cancer. Preliminary Results from the AHS-2 Cohort

Introduction: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen remains unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Materials/Methods: We evaluated the Surveillance Epidemiology and End Results (SEER) cancer incidence trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each five year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger population and those with EAC histology as previously demonstrated. EAC and ESCC incidence rates both increases with aging, consistent with cancer being an age-related disease, but the male: female incidence ratio of EAC significantly decreased with aging. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female cohort. Interestingly, the APC doubled in the last two age groupings of older females (age 65-74 = + 0.3 and age 75 and greater = + 0.7). APC rates for the males increased gradually in all their age groups (age 50-64 = +1.2, age 65-74 = +1.4, age 75+ = +1.9). Conclusions: The males’ incidence of EAC increases at a steep rate with aging and females’ incidence rates are not as steep except after age 60-64 where their incidence rate of change steeply increases. The steeper change in EAC incidence rates in the post menopausal female may explain why the male: female EAC incidence ratio decreases with age as seen nationally (SEER). The negative APC in the female 50-64 years age group may be explained by their peri-menopausal state and by the increased use of post-menopausal hormonal therapy since 1975 for this age group. Using age as a proxy for estrogen exposure, our findings suggest a hormonal component for the observed age-related, declining male to female EAC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that the pre-menopausal estrogen milieu in females may serve as a protective factor against EAC. Moreover, this protective state dissipates with time in the post menopausal females where the effect of estrogen exposure dissipates. Implications: Our initial epidemiological observation of gender-age differences warrants translation into a molecular epidemiology study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen exposure in esophageal adenocarcinoma. Citation Format: Luckson N. Mathieu, Norma Kanarek, Craig Hooker, Malcolm Brock. Gender disparity in esophageal cancer incidence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4802. doi:10.1158/1538-7445.AM2013-4802

BackgroundWorldwide, oesophageal cancer is one of the most common cancers and a leading cause of cancer mortality. Owing to its aggressive disease nature and poor survival rate, it contributes to...

Erratum: salt tea consumption and esophageal cancer: a possible role of alkaline beverages in esophageal carcinogenesis.

Esophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Esophageal adenocarcinoma (OAC), the predominant subtype in western countries, is largely resistant to current chemotherapy regimens. Selective markers are needed to enhance clinical staging and to allow targeted therapies yet there are minimal proteomic data on this cancer type. After histological review, lysates from OAC and matched normal esophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labeling and OFFGEL fractionation. Patient matched samples of OAC, normal esophagus, normal stomach, lymph node metastases and uninvolved lymph nodes were used from an additional 115 patients for verification of expression by immunohistochemistry (IHC).Over six thousand proteins were identified and quantified across samples. Quantitative reproducibility was excellent between technical replicates and a moderate correlation was seen across samples with the same histology. The quantitative accuracy was verified across the dynamic range for seven proteins by immunohistochemistry (IHC) on the originating tissues. Multiple novel tumor-specific candidates are proposed and EPCAM was verified by IHC.This shotgun proteomic study of OAC used a comparative quantitative approach to reveal proteins highly expressed in specific tissue types. Novel tumor-specific proteins are proposed and EPCAM was demonstrated to be specifically overexpressed in primary tumors and lymph node metastases compared with surrounding normal tissues. This candidate and others proposed in this study could be developed as tumor-specific targets for novel clinical staging and therapeutic approaches.

BackgroundRecent studies have indicated that the incidence of esophageal cancer has declined in the past decade in the U.S. However, trends in the incidence and survival have not been thoroughly examined.MethodsData from 46 063 patients with esophageal cancer between 1973 and 2015 were collected from the Surveillance, Epidemiology, and End Results database. The trends in the age‐adjusted incidence and survival were analyzed using joinpoint regression models.ResultsThe age‐adjusted incidence of esophageal cancer increased from 5.55 to 7.44 per 100 000 person‐years between 1973 and 2004. Later, it decreased at an annual percentage change of 1.23%. In the last 40 years, the strong male predominance increased slightly. Importantly, the percentage of patients with localized stage of squamous cell cancer decreased. It was observed that the incidence of esophageal squamous cell carcinoma declined since 1986, while the incidence of esophageal adenocarcinoma sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men. Consistently, the estimated 40‐year limited‐duration prevalence of esophageal adenocarcinoma was higher than that of esophageal squamous cell carcinoma. Additionally, we observed a modest but significant improvement in survival during the study period.ConclusionThe incidence of esophageal squamous cell carcinoma has decreased significantly over the past four decades in the U.S., while the incidence of adenocarcinoma has increased, particularly among men. Overall, the long‐term survival of patients with esophageal cancer is poor but it has improved over the past decades, especially for the localized disease.Key pointsSignificant findings of the studyThe incidence of esophageal cancer has decreased at an annual percentage change of 1.23% since 2004. The incidence of esophageal adenocarcinoma has sharply increased since 1973 and surpassed the rate of squamous cell cancer, mainly due to the increase in the incidence among men.What this study addsThere has been a shift in the prevalence of esophageal cancer histological subtypes over the past decades in the U.S. We found that the incidence of esophageal squamous cell carcinoma has continued to decrease, while the esophageal adenocarcinoma rate has continued to increase.

PurposeThis study aimed to provide a clear comparable figure of the trends in incidence and mortality rates of esophageal cancer (EC) in Huai’an District, Huai’an City, Jiangsu Province, China, a high-risk area for EC.MethodsThe data for age- and sex-specific incidence rates between 1998 and 2016, the mortality rates in 1990-2016 and the number of EC patients were obtained from Huai’an District Cancer Registry. Crude rates, Age-standardized rates (ASRs) by world standard population and truncated age-standardized rates of EC incidence and mortality were calculated. The joinpoint regression analysis was used to calculate the annual percent changes (APC), average annual percent changes (AAPC), and their 95% confidence intervals (CIs).ResultsOverall, 20,892 new EC cases and 20,806 EC deaths were registered in Huai’an District. ASR of EC incidence from 1998 to 2016 and mortality from 1990 to 2016 were 73.32/100,000 and 60.03/100,000, respectively. The ASR illustrated that the incidence of EC had significant downward trends in total, male and female (AAPC = −4.65, −4.90, and −5.51, respectively, p <.01). The age-specific incidence and mortality rates of EC increased dramatically in people over the age of 40, and peaked in people between the ages 70-74. In the subdivisions of Huai’an District, geographical diversities in the crude incidence and mortality rates of EC were found.ConclusionIn summary, the incidence and mortality rates of EC showed downward trends in Huai’an District. However, the burden of EC still remained serious in this high-risk area. Cost-effective methods of intervention and health education should be enhanced for improving EC prevention.

Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000–2018)

Low Incidence of Esophageal Adenocarcinoma After Eradication of Helicobacter pylori in Japan

47 Background: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen are unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Methods: We evaluated the SEER cancer incidence and trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each ten-year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger group and those with EAC histology. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female group. The negative APC in the female 50-64 years age group may be due to the increased use of exogenous hormonal therapy since 1975 for this age group. Interestingly, the APC was positive (increasing) in the 65+ age females. Conclusions: Using age as a proxy for estrogen exposure, our findings suggest a hormonal reason for the observed age-related, declining male to female EC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that estrogen may serve as a preventative agent against EC. Moreover, this protective role of estrogen may dissipate with time if post menopausal estrogen use is discontinued. We have initiated a subset analysis of the nine individual SEER sites’ database to confirm the above findings by location and plan to further assess the relationship of both endogenous and exogenous estrogen via hormonal therapy use in EC incidence in the Women’s Health Initiative cohort. Our epidemiological observation of gender-age differences warrants translation into a molecular study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen in esophageal cancer.

Patterns and trends in esophageal cancer incidence and mortality in China: An analysis based on cancer registry data

Esophageal cancer can present as two histological subtypes of esophageal cancer, adenocarcinoma or squamous cell carcinoma. The vast majority, if not all, esophageal adenocarcinomas arise from Barrett’s esophagus. Similarly, squamous dysplasia carries an elevated risk of progression to esophageal squamous cell carcinoma. Both cancer types have extremely poor survival rates, and therefore there is an acute need to identify modifiable risk factors that may help to prevent their development. Despite the mechanistic and ecological support for a general anti-carcinogenic role of vitamin D, studies in relation to esophageal cancer have illustrated conflicting results. Studies of vitamin D intake have been inversely associated with squamous cell carcinoma risk and directly associated with adenocarcinoma risk in European studies, while no significant associations were observed in an American case–control study. Contradictory to this, evidence from high quality prospective cohorts have illustrated that low levels of circulating vitamin D are associated with a reduced risk of esophageal squamous cell carcinoma, particularly in Asian populations. Small studies of vitamin D related genetic variants have failed to detect an association with the risk of either histological subtype of esophageal cancer. Laboratory investigations do suggest, however, that vitamin D receptor expression is more apparent in Barrett’s esophagus and esophageal adenocarcinoma tissue, and therefore are more likely to interact with vitamin D intake or status to impact on outcomes compared with squamous cell carcinomas. Whether these are positive or negative influences on development or survival remains unclear. Further work is clearly warranted in this area to fully understand the mechanisms involved and to clarify the conflicting evidence to date.