Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study

Abstract

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.

Construction of the Interaction Network of Hub Genes in the Progression of Barrett’s Esophagus to Esophageal Adenocarcinoma

“…There is growing evidence that the progression of BE to EAC is a multistep process that includes the development of non-developmental abnormal BE to low-grade atypical hyperplasia, then to high-grade atypical hyperplasia, and ultimately to EAC. [25][26][27] However, the molecular mechanism by which BE becomes cancerous is largely unknown. In BE is the only recognized precancerous lesion of EAC, and almost all EAC originates from BE.…”

Sex, Racial and Ethnic Differences in Barrett’s Esophagus and Epidemiology of Esophageal Cancer

“…In a recent multicenter prospective cohort study of 868 patients, the risk of neoplastic progression to high grade dysplasia and/or EAC was twice as high in men than women (HR: 2.3, 95% CI: 1.11-4.6). 12 Men also had a shorter time to neoplastic progression compared to women (2.1 year, IQR: 1.0-4.3 vs 4.6 year, IQR: 2.0-6.4). 12 In another meta-analysis, the rate of annual progression from BE to high grade dysplasia and/or EAC was 0.62%/year in women and 1.54%/ year in men (OR: 0.44, CI: 0.30-0.65).…”

“…12 Men also had a shorter time to neoplastic progression compared to women (2.1 year, IQR: 1.0-4.3 vs 4.6 year, IQR: 2.0-6.4). 12 In another meta-analysis, the rate of annual progression from BE to high grade dysplasia and/or EAC was 0.62%/year in women and 1.54%/ year in men (OR: 0.44, CI: 0.30-0.65). 17 In addition to male sex, other variables that have been identified as predictors for the neoplastic progression of BE are older age, a history of smoking, low-grade dysplasia and longer length of the BE segment.…”

“…8 Numerous studies have highlighted sex, racial, and ethnic disparities in the incidence, prevalence and outcomes of BE and EAC. 7,[9][10][11][12][13] These disparities partly occur due to historic and contemporary social and economic inequalities. A better understanding of the cause and nature of these disparities could help guide meaningful action toward mitigating modifiable factors that drive these differences.…”