Which factors best predict the risk of developing BO?
Which factors best predict the risk of developing BO?
Risk factors for Barrett’s Oesophagus (BO) have been assessed in more than 50 studies. All of the studies have been observational, and the vast majority to date have been case-control studies of varying degrees of quality. Several features of study design are likely to have contributed to differences in effect estimates between studies, particularly the ways in which BO cases and controls have been defined and selected. For example, a small number of studies have recruited only newly diagnosed BO cases, whereas others have recruited patients known to have pre-existing disease (‘prevalent cases’). Similarly, important differences are likely to exist between population versus institutional controls, and between ‘disease-free’ versus ‘reflux controls’. Other features include the quality of exposure measurements, the methods of analysis and control of potentially confounding factors. These elements of study quality must be borne in mind when assessing the evidence base. Wherever possible, estimates from higher quality studies have been used in the summaries below.
Risk factors for Barrett's Oesophagus
There is consistent observational evidence that patients with long-segment BO are much more likely (up to ten-fold in some reports) to report a past history of frequent (more than weekly) gastro-oesophageal acid reflux (GOR) symptoms than population controls. A systematic review of six high-quality observational studies reported a summary odds ratio of 4.92 (95% CI 2.01-12.0) for long segment BO and 1.15 (95% CI 0.763–1.73) for short segment BO.
The association between body mass index (BMI, a simple but crude measure of body mass adjusted for height) and risk of BO has been inconsistent across studies. Most studies have reported small, non-significant, positive associations. Measures of central adiposity (such as waist circumference, waist-hip ratio) and visceral obesity (such as computed tomography (CT) measures of abdominal fat) have been consistently reported to be significantly associated with moderately increased risks of BO. A pooled analysis of four population-based case-control studies comprising 1102 BO cases and 1400 population controls found no evidence of a significant association between BMI and the risk of BO. In contrast, that pooled analysis observed that persons in the highest versus the lowest quartiles of waist circumference had approximately 125% and 275% increases in the odds of BO among men and women, respectively (men OR 2.24, 95% CI 1.08 - 4.65; women OR 3.75, 95% CI 1.47 to 9.56). The associations with measures of central obesity persisted after adjusting for the confounding effects of BMI and gastro-oesophageal reflux. Similarly, a meta-analysis of 15 studies reported a summary OR of 1.98 (95% CI 1.52-2.57) for measures of central adiposity associated with BO.
Data from case-control studies consistently report risks of BO among smokers to be about 50-60% higher than non-smokers, after adjusting for other potentially confounding factors. A pooled analysis using primary data from five case-control studies (1059 BO cases, 1332 gastro-oesophageal reflux disease (GORD) controls, 1143 population controls) reported a summary odds ratio of 1.67 (95% CI 1.04-2.67) for ever versus never smoking when comparing BO cases to population controls, and OR 1.61 (95% CI 1.33-1.96) when compared to GORD controls. Similarly, a systematic review and meta-analysis of 39 studies comprising 7069 BO patients reported a summary odds ratio of 1.42 (95% CI 1.15-1.76) for ever versus never smoking when comparing BO cases to population controls.
A systematic review and meta-analysis of 32 studies providing a sex ratio for Barrett’s Oesophagus reported a summary ratio of 1.96 (95% CI 1.77-2.17). Although there was considerable heterogeneity in the magnitude of the ratio across studies (ratio ranges 1.08-4.43), all studies observed a male excess of BO.
Population studies suggest that the probability of a new diagnosis of Barrett’s Oesophagus increases with age. A US community study reported that the incidence of new Barrett’s Oesophagus was 7 per 100,000 person-years for people 21-30 years and 31 per 100,000 person-years for people aged 61-70 years (adjusted for the different endoscopy rates at different ages). Case-control studies estimate that the relative risk of diagnosis of Barrett’s Oesophagus increases by about 30% per decade above 40 years when compared against patients with a diagnosis of gastro-oesophageal reflux disease.
A limited number of case-control studies have conducted serological assays comparing the prevalence of anti-H pylori antibodies between BO cases and controls. These studies have typically reported risk reductions of about 50% for persons with evidence of past infection with H pylori..
There is no evidence that alcohol consumption increases the risk of BO. At least three high-quality case-control studies and one cohort study have examined this factor in detail and all reported null findings.
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs)
A very small number of observational studies have investigated possible associations between self-reported use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and risks of BO. There was no evidence that regular users of aspirin or NSAIDs differed in their risks of BO from never users.
There is no consistent evidence implicating any dietary or nutritional factors in altering a person’s risk of BO, however studies are few.
A small number of observational studies have investigated possible associations between metabolic factors and risks of BO. Some studies have reported modest positive associations with high levels of insulin and leptin, although findings are inconsistent across studies. Data for other factors (such as insulin-like growth factors) are scarce.
Hiatal hernias have been reported more frequently among patients with BO when compared against both patients with gastro-oesophageal reflux disease (GORD) (about a three-fold increased relative risk) and non-GORD controls (about a 13-fold increased relative risk).
A small number of studies has investigated the family history of patients with Barrett’s Oesophagus. These studies estimate that about 7% of patients with Barrett’s Oesophagus have a confirmed history of Barrett’s Oesophagus or oesophageal adenocarcinoma occurring in a first- or second-degree relative, equating to a relative risk about 12-fold higher than GORD controls.
Risk prediction tools for Barrett's Oesophagus
One study has developed a prediction tool to estimate the probability that a person has BO. The tool included terms for age, sex, smoking status, body mass index, education, and frequency of use of acid suppressant medications (area under the ROC curve, 0.70; 95%CI, 0.66–0.74). The model had moderate discrimination in an external dataset (area under the ROC curve, 0.61; 95%CI, 0.56–0.66).
Clinical studies have identified associations with obstructive sleep apnoea, although associations have been inconsistent across studies and residual confounding by other factors (notably obesity) cannot be excluded.
Evidence summary and recommendations
|Major risk factors for Barrett’s Oesophagus have been well characterised in population-based studies, and include age, male sex, history of frequent gastro-oesophageal acid reflux, abdominal obesity, smoking and family history.||III-3, IV||, , , , , , |
Issues requiring more clinical research study
- What is the role of aspirin/NSAIDs in the development of BO, and is chemoprevention possible?
- Are there any dietary factors that reduce the risk of BO?
- Is the apparent protective effect of Helicobacter infection causal? If so, what are the implications for clinical management?
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