Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma

Abstract

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.

Serum Sex Hormone Profiles in Potentially Resectable Esophageal Cancer

“…Recently, Xie, S-H et al found that an increased disease-specific mortality with lower SHBG levels and higher FSH levels in male EAC patients without surgical treatment. No clear associations were observed for dehydroepiandrosterone sulphate, LH, prolactin, testosterone, 17-OH-progesterone, progesterone, E2, androstenedione, testosterone:estradiol ratio or free testosterone index [46]. In our study, there was no correlation between sex hormones level and pathological features.…”

Identifying and Verifying AR, ERBB2, and VEGFA Are the Targets of Qigesan in the Treatment of Esophageal Adenocarcinoma In Silico and In Vitro

“…A research study suggested that hormones may be associated with high incidence rate of EAC in men [47]. Androgen receptor (AR) Scientific Programming is also commonly present in human tissues and is also seen in esophageal cancer [48]. Barrett's esophagus, a precancerous lesion of esophagus, has higher circulating levels of dihydrotestosterone (DHT) and testosterone than normal [49,50].…”

Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040

“…The causes for this gender difference in esophageal cancer are still unclear. Different exposure to high‐risk factors such as alcohol and tobacco, 20 , 21 hormonal influences, 22 , 23 and abdominal obesity, particularly in men, 24 probably led to this male predominance.…”