Manuscript word count (including references): 4,640 Summary word count: 244 Number of figures: 1 Number of tables: 3 Number of supplementary files: 4 Summary Background: Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable preclinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies

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... ave yet to assess the impact of ARB use on gastrooesophageal cancer survival. Aim: To investigate the association between post-diagnosis ARB use and gastro-oesophageal cancer survival. Methods: We selected a cohort of patients with newly-diagnosed gastro-oesophageal cancer between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used time-dependant Cox-regression models to calculate hazard ratios (HRs) comparing gastro-oesophageal cancer-specific mortality between post-diagnosis ARB users and nonusers, after adjusting for demographics, comorbidities and post-diagnosis aspirin or statin use. Results: Our cohort included 5,124 gastro-oesophageal cancer patients, of which 360 used ARBs, and 3,345 died due to their gastro-oesophageal cancer during follow-up. After adjustment, ARB users had moderately lower risk of gastro-oesophageal cancer mortality than the non-users (HR=0.83, 95% CI: 0.71, 0.98). There was evidence of a dose-response relationship with the lowest HRs observed among patients receiving at least two years of prescriptions (HR=0.42, 95% CI: 0.25, 0.72). Conclusions: In this large population-based gastro-oesophageal cancer cohort, we found moderately reduced cancer-specific mortality among ARB users. However, confirmation in further independent epidemiological studies with sufficient staging information is required. 309 obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. 310