Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma

Dong, Jingjing; Maj, Carlo; Tsavachidis, Spiridon; Ostrom, Quinn T.; Gharahkhani, Puya; Anderson, Lesley A.; Wu, Anna H.; Ye, Weimin; Bernstein, Leslie; Borisov, Oleg; Schröder, Julia; Chow, Wong‐Ho; Gammon, Marilie D.; Liu, Geoffrey; Caldas, Carlos; Pharoah, Paul D.P.; Risch, Harvey A.; May, Andrea; Gerges, Christian; Anders, Mario; Venerito, Marino; Schmidt, Thomas; Izbicki, Jakob R.; Hölscher, A. H.; Schumacher, Brigitte; Vashist, Yogesh K.; Neuhaus, Horst; Rösch, Thomas; Knapp, Michael; Krawitz, Peter; Böhmer, Anne C.; Iyer, Prasad G.; Reid, Brian J.; Lagergren, Jesper; Shaheen, Nicholas J.; Corley, Douglas A.; Gockel, Ines; Fitzgerald, Rebecca C.; Cook, Michael B.; Whiteman, David C.; Vaughan, Thomas L.; Schumacher, Johannes; Thrift, Aaron P.

doi:10.1053/j.gastro.2020.08.052

Cited by 21 publications

(12 citation statements)

References 98 publications

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“…Moreover, the genetic correlation between WHR and esophageal adenocarcinoma was significant in men, suggesting that the accumulation of VAT, which is more abundant in men than in women, is positively associated with EC incidence [83]. In addition, another genome-wide meta-analysis identified two female-specific and three male-specific loci associated with the risk of BE and esophageal adenocarcinoma, which could contribute to sex disparities in EC susceptibility [84].…”

Section: Genetic Factorsmentioning

confidence: 98%

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer

Heo

Kim

Sung

2021

IJMS

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Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.

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Section: Genetic Factorsmentioning

confidence: 98%

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer

Heo

Kim

Sung

2021

IJMS

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“…Several explanations can be proposed. First, recent studies have provided evidence that the androgen/estrogen balance may be a factor related to the development of EA in BE patients, in which higher levels of androgens relative to estrogens may favor cellular proliferation and tumor growth [28,29]. This would explain why males seem to develop neoplasia particularly faster compared to young/premenopausal females (with high levels of estrogens), but similarly to older/postmenopausal females (with lower levels of estrogens).…”

Section: Discussionmentioning

confidence: 99%

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

Roumans

Zellenrath

Lansdorp–Vogelaar

et al. 2022

Cancers

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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.

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“…The obesity group had a higher female proportion (71% vs. 60%), which may be a significant influence on some of the reported data. It should be noted that abdominal obesity and the breakdown of adipose tissue may contribute to the predominance of risk for malignancies, Barrett's esophagus or reflux, because it is associated with an increased risk of disease, regardless of body mass index (BMI) [25].…”

Section: Discussionmentioning

confidence: 99%

Role of Preoperative Esophagogastroduodenoscopy (EGD) in Bariatric Treatment

Sierżantowicz

Ładny

Kurek

et al. 2021

JCM

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Background: The recommendations for routine preoperative esophagogastroduodenoscopy (EGD) in patients qualified for bariatric surgeries are still a matter of debate. The aim of this study was to analyze the pathologies on preoperative EGD in patients qualified for bariatric surgeries. Materials and Methods: This study included 222 patients, divided into two groups. The obesity group consisted of patients with obesity (BMI ≥ 40 kg/m2), for whom EGD was a routine part of the preparation for laparoscopic sleeve gastrectomy (LSG). The control group of patients with normal body weight (BMI) qualified for EGD because of gastrointestinal ailments. Results: Regarding preoperative EGD in patients qualified for bariatric surgeries, we analyzed the prevalence of endoscopic pathologies in various gastrointestinal tract segments. Patients with obesity were shown to present with esophageal pathologies significantly more often than persons in the control group (n = 23, 20.91% vs. n = 12, 10.91%, p = 0.042). The odds ratio of esophageal pathologies in patients with obesity versus the control group equaled 2.15 (95%CI: 1.01–4.59). In turn, the odds ratio of duodenal pathologies in patients from the control group was 3.31 (95%Cl: 1.16–9.47), which means that persons from this group were approximately three times more likely to be diagnosed with those pathologies compared to obese patients. Moreover, patient sex was a significant predictor of duodenal pathologies, with an odds ratio of 4.03 (95%CI: 1.53–10.61). Conclusions: Preoperative EGD can identify a broad spectrum of pathologies in obese patients, which suggests a routine examination before bariatric surgery.

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Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma

Cited by 21 publications

References 98 publications

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer

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

Role of Preoperative Esophagogastroduodenoscopy (EGD) in Bariatric Treatment

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