The association between anxiety and esophageal cancer: A nationwide population‐based study

Abstract

Objective Research on generalized anxiety disorder (GAD) and its association with esophageal cancer (EC) is sparse. The study aimed to explore the association between GAD and EC. Methods A multicenter, population‐based study in high‐risk regions for EC (ECHRRs) was conducted from 2017 to 2019. All participants received free endoscopy screening. If the esophageal endoscopy results were suspicious, the pathological biopsy was performed to confirm normal, esophagitis, low‐grade intraepithelial neoplasia (LGIN), high‐grade intraepithelial neoplasia (HGIN), and EC. Information on participants' exposure to risk factors was collected. GAD was assessed with Generalized Anxiety Disorder Scale‐7. Results With esophageal endoscopy, 25,650 participants in ECHRRs were examined, 9586 of whom were suspicious and confirmed by esophageal pathology. The detection rate of EC and precancerous lesions was 6.83% (1751/25,650), with 1377 LGIN (5.37%), 272 HGIN (1.06%), and 102 EC (0.40%) cases. The overall mean GAD score (95% CI) and prevalence among 25,650 participants with endoscopy were 1.96 (1.93–1.99) and 16.90%, respectively. The mean GAD score and prevalence among 9586 participants with pathology were 1.96 (1.91–2.02) and 17.98%, respectively. The mean GAD scores of patients confirmed with normal, esophagitis, LGIN, HGIN, and EC were 1.73 (1.62–1.85), 1.91 (1.85–1.97), 1.94 (1.80–2.08), 3.98 (3.73–4.23). and 2.97 (2.49–3.45), respectively (p < 0.001). The corresponding prevalence of GAD were 5.21%, 18.72%, 17.72%, 43.75%, and 36.27%, respectively (p < 0.001). The age‐ and gender‐adjusted odds ratios (ORs) between GAD and each esophageal lesion type were 1.02 (0.99–1.04), 1.01 (0.98–1.04), 1.27 (1.21–1.33), and 1.16 (1.08‐1.24), respectively. The ORs (95% CIs) of the positive associations were 1.08 (1.05–1.12), 1.03 (0.99–1.07), 1.35 (1.29–1.42), and 1.19 (1.10–1.29) after further adjustment for potential confounders (all p < 0.001). Sensitivity analysis showed that the positive association persisted. Conclusions GAD was significantly higher in patients with EC and precancerous lesions. Focusing on and alleviating anxiety in high‐risk groups (including patients with HGIN and EC) may be an effective strategy for EC prevention and control. Further prospective studies are warranted to validate the results.

Biological correlates before esophageal cancer screening and after diagnosis

“…The possible explanation was that cancer-related diagnosis in screening might act as a severe stressor and stimulation of life-stress events, especially for patients screened as HGIN and EC. They were susceptible to fall into a gloomy, depressed, and painful mood 13 – 15 . The plausible biological mechanisms have been proposed that stressor stimulates and imbalances the hypothalamic–pituitary–adrenal axis (HPA).…”

“…The main reason was that LGIN diagnosis might be a stressful life event and a potential stimulus, especially for precancerous lesions. When high-risk states are screened, the patient may be hard to accept for a short time and may get distressed about cancer progression, treatment, recurrence, and metastasis 13 . The precancerous diagnosis activated the HPA, secreted cortisol excessively, and weakened the body’s immune function through the neuro-endocrine-immune network abnormally 35 , 36 .…”

“…The impact of cancer screening has long been a controversial topic according to its benefits and disadvantages. Although several EC screening programs in high prevalence regions of China have demonstrated the efficacy of endoscopic screening in reducing the incidence and mortality of EC 5 – 8 , false-positive results, over-diagnosis, psychological burden, and biological change due to cancer screening are increasingly recognized 9 – 13 .…”

A Population-Based Study: How to Identify High-Risk T1–2 Esophageal Cancer Patients?

“…2021), T1-2 ESCA has been defined to invade lamina propria, muscularis mucosae, submucosa, or muscularis propria, but not to invade fibrous membrane (2). For patients with newly diagnosed esophageal space-occupying lesions, their pathological diagnosis is often made by endoscopic biopsy (3). Most of T1-2 ESCA patients do not have LNM and DM at the initial diagnosis, but some of them suffer LNM and/or DM (4)(5)(6).…”

Data_Sheet_1.PDF

“…In this case, it is difficult for patients to accept the fact in a short time, which may act as a serious stressor and stimulation of life-stress events, especially for patients who have been screened for EC and precancerous lesions. Considering cancer progression, recurrence, and prognosis, they are prone to distress (26).…”