Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study.

BACKGROUND: We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. METHODS: This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. RESULTS: Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). CONCLUSION: This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site.

BACKGROUND: To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site. METHODS: A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed. RESULTS: The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82-1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80-1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39-0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37-0.65). CONCLUSION: Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.

Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men.

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 patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 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-OH progesterone, 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 vs lowest quartile = 0.60, 95% CI 0.38-0.97), whereas no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. DISCUSSION: Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.

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.

Circulating Levels of Inflammatory and Metabolic Biomarkers and Risk of Esophageal Adenocarcinoma and Barrett Esophagus: Systematic Review and Meta-analysis.

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 adenocarcinoma), 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 TNFα. 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.