Sex differences in esophageal cancer overall and by histological subtype

Abstract

Esophageal cancer is the seventh most common type of cancer in the world, the sixth leading cause of cancer-related death and its incidence is expected to rise 140% in the world in a period of 10 years until 2025. The overall incidence is higher in males, while data about prognosis and survival are not well established yet. The goal of this study was to carry out a comprehensive analysis of differences between sexes and other covariates in patients diagnosed with primary esophageal cancer. Data from 2005 to 2020 were obtained from the University Hospitals (UH) Seidman Cancer Center and from 2005 to 2018 from SEER. Patients were categorized according to histological subtype and divided according to sex. Pearson Chi-square test was used to compare variables of interest by sex and the influence of sex on survival was assessed by Kaplan Meier, log rank tests and Cox proportional hazards regression models. A total of 1205 patients were used for analysis. Sex differences in all types were found for age at diagnosis, histology, smoking status and prescriptions of NSAIDs and in SCC for age at diagnosis and alcoholism. Survival analysis didn't showed differences between males and females on univariable and multivariable models. Males have a higher incidence of Esophageal Cancer and its two main subtypes but none of the comprehensive set of variables analyzed showed to be strongly or unique correlated with this sex difference in incidence nor are they associated with a sex difference in survival.

Figure 1

Cohort description with inclusion and exclusion criteria for UH institutional database. The final cohort included 1205 patients diagnosed with esophageal cancer from 2005 to 2020 with ≥ 18 years, excluding those without unknown diagnosis date, missing gender and without primary esophageal cancer).

Figure 2

Plots of cases by year from UH Seidman Cancer Center (2005–2020) and SEER (2005–2018) for all types of esophageal cancer, esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC). All types of esophageal cancer cases are increasing in the US.

Figure 3

Forest plot of sex differences in survival for esophageal cancer (all types), esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC). Univariable and multivariable cox models represented, UH Seidman Cancer Center Database (2005–2020). *Adjusted for: age at diagnosis, race, ethnicity, histology, obesity, Barret’s, gastrectomy, gastritis, gastroesophageal reflux, chemotherapy, surgery and radiotherapy. **Adjusted for: age at diagnosis, smoking status, obesity, Barret’s, alcoholism, achalasia, gastrectomy, gastritis, gastroesophageal reflux, h.pilory, chemotherapy, surgery and radiotherapy. ***Adjusted for: race, Barret’s, gastritis, gastroesophageal reflux, h.pilory, radiotherapy, surgery, smoking status and alcoholism.

Figure 4

Sex differences for esophageal cancer overall. Higher in males (3:1 ratio) and statistical differences for age at diagnosis (p < 0.001), smoking status (p = 0.01), histological subtype (p < 0.001) and NSAIDs use (p = 0.04), UH Seidman Cancer Center Database (2005–2020).

Figure 5

Sex differences for esophageal adenocarcinoma (EAC). Higher in males (ratio 4:1), UH Seidman Cancer Center Database (2005–2020).

Figure 6

Sex differences for squamous cell carcinoma (SCC). Higher in males (ratio 3:2) and statistical differences in age a diagnosis (p = 0.02) and alcoholism (p = 0.04), UH Seidman Cancer Center Database (2005–2020).

Figure 7

Forest plot of sex differences in survival for esophageal cancer (all types), esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC). Univariable and multivariable cox models represented, SEER Database (2005–2018). *Adjusted for: age at diagnosis, race, ethnicity, histology, stage, chemotherapy, radiotherapy, and surgery. **Adjusted for: age at diagnosis, race, ethnicity, stage, chemotherapy, radiotherapy, and surgery. ***Adjusted for: age at diagnosis, race, histology, stage, chemotherapy, radiotherapy, and surgery.