Introduction Barrett's oesophagus is the result of chronic gastro-oesophageal reflux disease (GORD) and is associated with the development of oesophageal adenocarcinoma (OAC). We have undertaken the largest case-control study to date to examine the relationship between GORD symptoms and the development of OAC.

Methods Incident cases of OAC from 12 hospitals in the Midlands, UK and age-, gender-, ethnically- and geographically-matched community control (CC) subjects (from primary care) and reflux oesophagitis (RO) control patients (from endoscopy units) were recruited and interviewed. Logistic regression generated odds ratios (OR) for duration, frequency and nocturnal symptoms of heartburn and acid regurgitation 1 and 10 years prior to diagnosis of OAC or interview for the study for controls.

Results 207 OAC (177 men, median (IQR) age 68 (60–75) years), 283 CC subjects (236 men, age 67 (60–74) years), and 224 RO patients (178 men, age 66 (59–75) years) were recruited. The presence of GORD symptoms was associated with OAC vs CC: OR (95% CI) 2.83 (1.94 to 4.14) (p<0.0001), but there was no difference vs RO. A longer duration of heartburn was associated with OAC: vs CC 3.36 (1.6–7.04) (p=0.001) and vs RO 5.24 (2.41–11.38) (p<0.0001). A longer duration of acid regurgitation was also associated with OAC: vs CC 2.95 (1.22–7.14) (p=0.017) and vs RO 9.16 (3.88-21.66) (p<0.0001). Increasing frequency of GORD symptoms was also associated with OAC vs CC: 1 year prior to diagnosis – daily heartburn 2.96 (1.38–6.34) (p=0.005), daily acid regurgitation 11.66 (2.6-52.16) (p=0.001); 10 years prior to diagnosis – daily heartburn 2.66 (1.29–5.46) (p=0.008); and OAC vs RO, but only 10 years prior – daily heartburn 2.02 (1.1-3.71) (p=0.023). Nocturnal GORD symptoms were associated with OAC vs CC: 1 year prior to diagnosis acid regurgitation 2.25 (1.29–3.92) (p=0.004); 10 years prior to diagnosis heartburn 2.03 (1.2–3.43) (p=0.008) and acid regurgitation 2.19 (1.22–3.92) (p=0.009); and vs RO 10 years prior to diagnosis – heartburn 3.39 (1.98–5.78) and acid regurgitation 3.94 (2.23–6.98) (both p<0.0001). Finally, antacid usage was also associated with OAC 10 years prior to diagnosis: vs CC 1.92 (1.5–2.46) (p<0.0001) and vs RO 1.34 (1.06–1.68) (p=0.014).

Conclusion Subjects with GORD symptoms are at increased risk of developing OAC. The increased risk of developing OAC is most marked in those whose symptoms occur daily, who have had symptoms for at least 10 years, who have required antacids for 10 years and whose symptoms wake them from sleep.