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.

Objectives: Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. Methods:This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male esophageal adenocarcinoma patients and 244 male agematched control participants. Associations between pre-diagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. Additionally, a random-effect meta-analysis combined these data with a similar prospective study for five sex hormones.Results: Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR=0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR=0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR=0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR=0.56, 95% CI 0.27-1.13 for testosterone; OR=0.46, 95% CI 0.23-0.91 for testosterone:estradiol ratio; OR=0.55, 95% CI 0.29-1.08 for luteinizing hormone). No associations were observed for sex hormone-binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OHprogesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest versus lowest quartile=0.60, 95% CI 0.38-0.97), while no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. Conclusions:Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men. Study highlights 1. WHAT IS CURRENT KNOWLEDGE? Esophageal adenocarcinoma is characterized by an extreme and unexplained male predominance in incidence. Sex hormones may explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. How endogenous sex hormone levels influence esophageal adenocarcinoma risk warrants investigation in prospective studies. WHAT IS NEW HERE? This was a case-control study nested in a prospective Norwegian cohort (Janus Serum Bank Cohort). We assessed associations between pre-diagnostic sex hormone levels and esophageal adenocarcinoma risk in men. Decreased esophageal adenocarcinoma risk was associated with higher testosterone, luteinizing hormone, and testosterone:estradiol ratio levels. These associations were attenuated after adjustment for body mass index. A meta-analysis confirmed a decreased risk of esophageal/gastric cardia adenocarcinoma associated with higher testosterone levels.

Associations between circulating levels of obesity-related biomarkers and risk of esophageal adenocarcinoma and Barrett esophagus have been reported, but the results are inconsistent. A literature search until October 2018 in MEDLINE and EMBASE was performed. Pooled ORs with 95% confidence intervals (CI) were estimated for associations between 13 obesity-related inflammatory and metabolic biomarkers and risk of esophageal adenocarcinoma or Barrett esophagus using random effect meta-analyses. Among 7,641 studies, 19 were eligible for inclusion (12 cross-sectional, two nested case-control, and five cohort studies). Comparing the highest versus lowest categories of circulating biomarker levels, the pooled ORs were increased for leptin (OR, 1.68; 95% CI, 0.95-2.97 for Barrett esophagus), glucose (OR, 1.12; 95% CI, 1.03-1.22 for esophageal adenocar-cinoma), insulin (OR, 1.47; 95% CI, 1.06-2.00 for Barrett esophagus), C-reactive protein (CRP; OR, 2.06; 95% CI, 1.28-3.31 for esophageal adenocarcinoma), IL6 (OR, 1.50; 95% CI, 1.03-2.19 for esophageal adenocarcinoma), and soluble TNF receptor 2 (sTNFR-2; OR, 3.16; 95% CI, 1.76-5.65 for esophageal adenocarcinoma). No associations were identified for adiponectin, ghrelin, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, triglycerides, IL8, or TNFa. Higher circulating levels of leptin, glucose, insulin, CRP, IL6, and sTNFR-2 may be associated with an increased risk of esophageal adenocarcinoma or Barrett esophagus. More prospective studies are required to identify biomarkers that can help select high-risk individuals for targeted prevention and early detection.