Shao-Hua Xie

The Male Predominance in Esophageal Adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has increased rapidly during the past 4 decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastroesophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9:1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, whereas androgens might increase the risk of EAC. However, continuing research efforts are still needed to fully understand the reasons for the male predominance of EAC.

A model for predicting individuals’ absolute risk of esophageal adenocarcinoma: Moving toward tailored screening and prevention

Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and poor prognosis, stressing the need for preventive and early detection strategies. We used data from a nationwide population‐based case‐control study, which included 189 incident cases of EAC and 820 age‐ and sex‐matched control participants, from 1995 through 1997 in Sweden. We developed risk prediction models based on unconditional logistic regression. Candidate predictors included established and readily identifiable risk factors for EAC. The performance of model was assessed by the area under receiver operating characteristic curve (AUC) with cross‐validation. The final model could explain 94% of all case patients with EAC (94% population attributable risk) and included terms for gastro‐esophageal reflux symptoms or use of antireflux medication, body mass index (BMI), tobacco smoking, duration of living with a partner, previous diagnoses of esophagitis and diaphragmatic hernia and previous surgery for esophagitis, diaphragmatic hernia or severe reflux or gastric or duodenal ulcer. The AUC was 0.84 (95% confidence interval [CI] 0.81–0.87) and slightly lower after cross‐validation. A simpler model, based only on reflux symptoms or use of antireflux medication, BMI and tobacco smoking could explain 91% of the case patients with EAC and had an AUC of 0.82 (95% CI 0.78–0.85). These EAC prediction models showed good discriminative accuracy, but need to be validated in other populations. These models have the potential for future use in identifying individuals with high absolute risk of EAC in the population, who may be considered for endoscopic screening and targeted prevention.

Time trends in the incidence of oesophageal cancer in Asia: Variations across populations and histological types

OBJECTIVE We aimed to assess temporal trends in incidence rates of oesophageal cancer in Asian countries. MATERIALS AND METHODS Using data from the Cancer Incidence in Five Continents series, we examined the temporal trends in incidence rates of oesophageal cancer by population and histological type in seven Asian countries in 1988-2007. Age-period-cohort analyses estimated the overall annual percentage changes (net drifts) and their 95% confidence intervals (CIs) in incidence rates. RESULTS The age-standardised incidence rate of oesophageal cancer declined in most Asian populations, but remained relatively unchanged in Japan and Israel. The rate of oesophageal squamous cell carcinoma decreased in Hong Kong, Singapore and Israel, but was stable in Japan. The net drifts were statistically significant in men in Hong Kong (-3.4%, 95% CI: -6.1%, -0.7%) and in women in Singapore (-10.1%, 95% CI: -14.4%, -5.5%). The age-standardised incidence rates of oesophageal adenocarcinoma were below 2 and 0.5 per 100 000 in men and women, respectively, across all periods in the all registers containing valid data on histological type. The age-standardised incidence rate of oesophageal adenocarcinoma slightly increased in Japan, Singapore, and Israel, although the net drift was statistically significant only in Israeli men (4.9%, 95% CI: 0.8%, 9.1%). CONCLUSION The overall incidence rates of oesophageal cancer declined in most Asian countries, which is due to a decrease in oesophageal squamous cell carcinoma incidence. However, attention needs to be paid to a probable beginning of an increasing incidence of oesophageal adenocarcinoma in Asia.

Incidence trends in oesophageal cancer by histological type: An updated analysis in Sweden

BACKGROUND We aimed to update incidence trends of oesophageal cancer by histological type in Sweden. METHODS Using data from the Swedish Cancer Registry, we examined incidence trends of oesophageal cancer by histological types in individuals aged ≥50 years in 1970-2014 using log-linear joinpoint regressions. RESULTS The age-standardised incidence rate of oesophageal adenocarcinoma in men increased on average by 3.0% per year in 1970-1994, followed by a more rapid increase of 13.7% per year in 1994-2000, and a slower increase of 2.6% per year in 2010-2014. The rate of oesophageal adenocarcinoma in women increased on average by 4.2% per year during the entire period. The rate of squamous cell carcinoma generally decreased over the past 2-3 decades in both sexes. CONCLUSIONS The incidence of oesophageal adenocarcinoma continues to rise in Sweden, although the increase seems to have slowed down in men since 2000. The incidence of oesophageal squamous cell carcinoma is decreasing.

A global assessment of the male predominance in esophageal adenocarcinoma.

Background Esophageal adenocarcinoma (EAC) is characterized by a male predominance. However, variations in the sex difference across populations and over time have not previously been thoroughly investigated. Results The male-to-female ratio in EAC incidence varied greatly across continents, ranging from 1.03 in Africa to 7.64 in Northern America during 2003– 2007. The ratio was high in Europe (6.04) and Oceania (6.24), and lower in Asia (4.37) and Latin America and the Caribbean (3.94). The sex ratio remained relatively stable over time in most populations. In absolute terms, the sex difference in EAC incidence increased over time in populations of higher incidence, while it remained stable or slightly decreased in low-incidence populations. Materials and Methods We used data from the Cancer Incidence in Five Continents series to compute sex-specific age-standardized rates of EAC by population. The sex difference in incidence was evaluated on both absolute and relative scales, measured by the absolute difference and ratio between sexes, respectively. Conclusions This first global assessment of the sex ratio in EAC shows that the male predominance is particularly strong in developed countries. The underlying reasons remain to be identified, but the emerging EAC burden in men merits consideration for targeted prevention and early detection.

Smoking cessation and risk of esophageal cancer by histological type : systematic review and meta-analysis

Background Tobacco smoking strongly increases risk of esophageal squamous cell carcinoma and moderately increases risk of esophageal adenocarcinoma. How smoking cessation influences esophageal cancer risk across histological subtypes, time latencies, and geographic regions is not clear. Methods Studies were systematically searched on Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Pooled estimates of risk ratios (RRs) were derived using a random effects model. Cochrans Q test and I2 statistic were used to detect heterogeneity. Results Among 15 009 studies, 52 fulfilled the inclusion criteria. Using nonsmokers as a reference, risk of esophageal squamous cell carcinoma was lower among former smokers (RR = 2.05, 95% confidence interval [CI] = 1.71 to 2.45) than among current smokers (RR = 4.18, 95% CI = 3.42 to 5.12). Compared with current smokers, a strong risk reduction was evident after five or more years (RR = 0.59, 95% CI = 0.47 to 0.75), and became stronger after 10 or more years (RR = 0.42, 95% CI = 0.34 to 0.51) and 20 or more years (RR = 0.34, 95% CI = 0.25 to 0.47) following smoking cessation. The risk reduction was strong in Western populations, while weak in Asian populations. Using nonsmokers as reference, the risk of esophageal adenocarcinoma was only slightly lower among former smokers (RR = 1.66, 95% CI = 1.48 to 1.85) than among current smokers (RR = 2.34, 95% CI = 2.04 to 2.69). The risk of esophageal adenocarcinoma did not show any clear reduction over time after smoking cessation, with a risk ratio of 0.72 (95% CI = 0.52 to 1.01) 20 or more years after smoking cessation, compared with current smokers. Conclusions Smoking cessation time-dependently decreases risk of esophageal squamous cell carcinoma, particularly in Western populations, while it has limited influence on the risk of esophageal adenocarcinoma.

Cause of death in patients diagnosed with esophageal cancer in Sweden: a population-based study

Background Esophageal cancer carries a poor prognosis with an overall 5-year survival of less than 20%. However, the causes of death in patients with esophageal cancer have not been well described. Methods This nationwide, population-based cohort study included 18 229 esophageal cancer patients who were diagnosed between 1961 and 2014 in Sweden. We assessed the distribution of main causes of death in patients with esophageal cancer and used competing-risks regression to compare the cause-specific risks of death across sexes, ages at diagnosis, and calendar periods of diagnosis. Results A total of 16 938 (92.9%) patients died during follow-up. Esophageal cancer accounted for 79.5% of all reported deaths. Other major causes of death were non-esophageal cancers (9.8%), ischemic heart disease or cerebrovascular disease (4.2%) and respiratory diseases (1.3%). Female patients had a lower risk of death from esophageal cancer (sub-hazard ratio [SHR]=0.90, 95% confidence interval [CI]: 0.87, 0.94), which was more pronounced in patients with squamous cell carcinoma (SHR=0.85, 95% CI: 0.81, 0.89). Risks of death from esophageal cancer and other cancers in patients who were diagnosed in more recent calendar periods were lower than in those diagnosed in earlier periods. Conclusions Patients diagnosed with esophageal cancer are more likely to die from this cancer than from other causes. However, these patients also face considerable risk of death from other cancers, ischemic heart disease, cerebrovascular disease, and respiratory diseases. These common causes of death should be taken into consideration in esophageal cancer management.BACKGROUND Esophageal cancer carries a poor prognosis with an overall 5-year survival of less than 20%. However, the causes of death in patients with esophageal cancer have not been well described. METHODS This nationwide, population-based cohort study included 18 229 esophageal cancer patients who were diagnosed between 1961 and 2014 in Sweden. We assessed the distribution of main causes of death in patients with esophageal cancer and used competing-risks regression to compare the cause-specific risks of death across sexes, ages at diagnosis, and calendar periods of diagnosis. RESULTS A total of 16 938 (92.9%) patients died during follow-up. Esophageal cancer accounted for 79.5% of all reported deaths. Other major causes of death were non-esophageal cancers (9.8%), ischemic heart disease or cerebrovascular disease (4.2%) and respiratory diseases (1.3%). Female patients had a lower risk of death from esophageal cancer (sub-hazard ratio [SHR]=0.90, 95% confidence interval [CI]: 0.87, 0.94), which was more pronounced in patients with squamous cell carcinoma (SHR=0.85, 95% CI: 0.81, 0.89). Risks of death from esophageal cancer and other cancers in patients who were diagnosed in more recent calendar periods were lower than in those diagnosed in earlier periods. CONCLUSIONS Patients diagnosed with esophageal cancer are more likely to die from this cancer than from other causes. However, these patients also face considerable risk of death from other cancers, ischemic heart disease, cerebrovascular disease, and respiratory diseases. These common causes of death should be taken into consideration in esophageal cancer management.

A possible link between famine exposure in early life and future risk of gastrointestinal cancers: Implications from age-period-cohort analysis.

The Chinese famine in 1958–1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983–2007, we calculated age‐specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non‐exposed reference cohort. Age‐period‐cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver and colorectal cancers was particularly high in men exposed to famine during early childhood (0–9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.

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.

Social group disparities in the incidence and prognosis of oesophageal cancer

There are substantial disparities in the incidence and prognosis of oesophageal cancer across social population groups, including sex, race/ethnicity, geographical location and socio-economic status. Both squamous cell carcinoma and adenocarcinoma of the oesophagus are more common in men than in women, but the male predominance in adenocarcinoma is stronger and less well understood. The varying incidence and prognosis of oesophageal cancer across racial/ethnic groups show distinct patterns by histological type. Individuals residing in rural areas have a higher incidence and worse prognosis than those in urban areas in developing regions. Lower socio-economic status is associated with an increased incidence and reduced survival in oesophageal cancer. Sustained research identifying novel preventive and therapeutic strategies are needed to reduce the risk of oesophageal cancer and improve the prognosis in all social groups.