AbstractGastro-oesophageal cancer is a major health problem. The overall objectives of this thesis were to investigate novel risk factors for gastro-oesophageal cancer risk and progression, in particular focusing on commonly used medications, sex hormones, hormonal and reproductive factors.
In vitro experiments have shown furosemide inhibited gastro-oesophageal cancer cell proliferation. However, the association between furosemide use and gastro- oesophageal cancer survival in humans has not been studied. A cohort study using UK primary care records from the Clinical Practice Research Datalink (CPRD) database was conducted to examine this association and found furosemide did not improve gastro-oesophageal cancer survival. Also within the CPRD database, use of medications with sex hormonal effects in relation to gastro-oesophageal cancer progression was examined with a particular focus on hormonal replacement therapy (HRT) because published reviews have suggested HRT should not be used in patients with gastric cancer. This thesis did not show any evidence that HRT was associated with worse survival in patients with gastro-oesophageal cancer.
The current thesis conducted a nested case-control study using Primary Care Clinical Informatics Unit (PCCIU) database and a cohort study using the UK Biobank to assess the association between acid-suppression therapy and gastro-oesophageal cancer risk. The finding showed an increased risk of gastro-oesophageal cancer in patients using proton pump inhibitors and/or histamine-2 receptor antagonists but, particularly for gastric cancer, these associations appeared consistent with confounding by indications rather than a real causal association.
The apparent sex-disparities in gastro-oesophageal cancer risk remain largely unexplained. The current thesis investigated pre-diagnostic circulating sex hormones and gastro-oesophageal cancer risk using the UK Biobank, and showed sex hormone binding globulin was positively associated with gastric cancer risk in men and suggested a role of testosterone in oesophageal cancer. Also, this thesis explored a variety of female reproductive factors in relation to the risk of gastro-oesophageal cancer mortality in the China Kadoorie Biobank. Only higher number of pregnancies and induced abortions were found to be associated with reduced risk of gastric cancer mortality.
In summary, the current thesis has contributed to the literature by identifying exposures which could influence gastro-oesophageal cancer risk and progression. Future studies are required to replicate the novel associations observed.
Thesis embargoed until 31 December 2022.
|Date of Award||Dec 2021|
|Sponsors||China Scholarship Council|
|Supervisor||Christopher Cardwell (Supervisor), Helen Coleman (Supervisor) & Úna McMenamin (Supervisor)|
- Gastric cancer
- oesophageal cancer
- risk factor