Introduction

The incidence of oesophago-gastric cancer has an age-dependent male predominance mirroring physiological changes in sex hormonal levels. Some previous studies suggest that menopausal hormone therapy (MHT) counteracts the occurrence of these tumours, but larger studies with longer follow-up and adjustment for confounders are needed, which prompted the present study.

Aims & Methods

To investigate the hypothesis that MHT decreases the risk of developing oesophago-gastric cancer, especially oesophageal adenocarcinoma.
This population-based case-control study included women aged ≥45 years in all five Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) between 1995-2020. Prospectively collected data came from national complete registries for medications, cancer, diagnoses, total populations, and death. The study included 19,518 case patients with oesophago-gastric cancer and 195,094 randomly identified control participants matched for age, country and calendar year. The participants were categorised into three equal-sized groups (tertiles) of defined daily doses (DDD) of MHT, with non-users as the reference group. MHT was also categorized as systemic or local, and oestrogen only or oestrogen combined with progesterone MHT. Oesophago-gastric cancer was divided into oesophageal or cardia adenocarcinoma, oesophageal squamous cell carcinoma, and gastric non-cardia adenocarcinoma as separate outcomes. Conditional logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, calendar year, country, obesity, gastroesophageal reflux disease, smoking, alcohol, Helicobacter pylori eradication, use of statins and non-steroidal anti-inflammatory drugs.

Results

​Compared to non-users of MHT, the adjusted ORs of oesophageal or cardia adenocarcinoma were 0.74 (95% CI 0.67-0.81) for low MHT-use (<158 DDDs), 0.68 (95% CI 0.61-0.75) for intermediate MHT-use (158-848 DDDs), and 0.68 (95% CI 0.61-0.75) for high MHT-use (>848 DDDs). The corresponding ORs were 0.69 (95% CI 0.62-0.77), 0.70 (95% CI 0.62-0.77), and 0.71 (95% CI 0.64-0.79) for oesophageal squamous cell carcinoma, and 0.90 (95% CI 0.84-0.96), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86) for gastric non-cardia adenocarcinoma.

Table. Odds ratios (OR) and 95% confidence intervals (CI) of oesophago-gastric cancer by tertiles of defined daily doses (DDD) of menopausal hormone therapy (MHT), MHT hormonal constitution and administration of MHT.

Conclusion

This study provides support for the hypothesis of an inverse association between MHT and risk of developing oesophago-gastric cancer, and particularly for oesophageal adenocarcinoma where the association was seemingly dose-dependent and stronger for combined oestrogen and progesterone MHT and for systemic MHT. A limitation to the study was the inability to adjust for socioeconomic factors as confounders.

Introduction

Screening for early oesophageal adenocarcinoma (OAC) has the potential to reduce OAC-related mortality and morbidity. However, it is unknown which screening method and/or eligibility criteria the target population would find acceptable for a potential future screening program.

Aims & Methods

In this ongoing online population-based survey, we aim to identify Dutch individuals’ perceived barriers and facilitators to the uptake of OAC screening and their preferences regarding screening method and organization. We aim to include 2088 Dutch adults aged 45-75 years, who will be randomly assigned to three screening test scenarios (i.e., transnasal endoscopy, ingestible cell-collection device, or breath analysis). The primary outcome is intended participation. Secondary outcomes include anticipated discomfort, acceptability of test performance and eligibility criteria (on a Likert scale: 1 = not acceptable, 7 = extremely acceptable), and preferences regarding invitation, counselling, and diagnostic follow-up. Enrolment will end in June 2023.

Results

As per 12 April, 1653 participants have been included (49% male, 96% white, 22% with upper endoscopy experience). Preliminary analyses show that intended uptake of screening was highest in the breath analysis scenario (97%), followed by ingestible cell-collection devices (76%), and transnasal endoscopy (68%) (p<0.001). Having symptoms of gastro-oesophageal reflux disease (GORD) and having a high perceived risk of OAC are both associated with a positive intention to participate in screening. High anticipated discomfort and having negative beliefs about cancer screening are associated with negative intent. Across all test scenarios, both age and GORD were acceptable eligibility criteria to most participants (mean scores of 5.4 [±1.5] and 5.2 [±1.7]). Inviting only men was less acceptable to women (3.9 [±2.0]) than to men (5.2 [± 1.9]). Using a risk algorithm was generally accepted (5.1 [±1.6]), and most individuals were willing to provide personal information (e.g., on smoking: 6.3 [±1.1], skin colour: 6.2 [±1.2], family history: 6.1 [±1.2], waist circumference: 5.9 [±1.4], or access to medical file: 5.7 [±1.5]), and a blood sample (6.1 [±1.2]). The majority (61%) preferred to be invited by a public health organization and 34% of the participants preferred to discuss their decision to participate in screening with a health care professional.

Conclusion

These preliminary results suggest that Dutch individuals generally intend to participate in OAC screening, with a preference for the breath analysis test/non-invasive screening methods over cell-collection devices and transnasal endoscopy. Determining screening eligibility based on age, GORD, or personal information, would be acceptable to most individuals. Male gender appears to be the least acceptable eligibility criterion.

Disclosure

JS, LR, FM, MB, and YP have no conflicts of interest or financial ties related to this work to disclose. PS is receiving unrestricted research grants from Pentax (Japan), Norgine (UK), Motus GI (USA), MicroTech (China) and The eNose Company (Netherlands) and is in the advisory board of Motus GI (US) and Boston Scientific (US).