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Title: Prior medical history, drug exposure and risk of multiple myeloma
Author: McShane, Charlene
ISNI:       0000 0004 5370 7667
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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To date, very little is known about the aetiology of the plasma cell disorder multiple myeloma (MM) and its precursor condition monoclonal gammopathy of undetermined significance (MGUS). Chronic antigenic stimulation and, more recently, medications have been investigated as potential aetiological risk factors however findings from observational studies have been largely inconsistent. This thesis aimed to explore the impact of medical history and drug exposure on the risk of developing MGUS and MM. A systematic review of the literature revealed an elevated risk of MGUS/MM in association with prior autoimmune disease and in particular pernicious anaemia. The findings of this study were further supported by a population-based nested case-control study carried out within the UK Clinical Practice Research Oatalink (CPRO). Similarly an increased risk of MGUS and MM following exposure to common community-acquired infections was observed within studies carried out within the CPRO and the USA SEER-Medicare dataset. Autoimmune disease and infections diagnosed after MGUS were not associated with progression to MM or associated Iymphoproliferative disorders within the CPRO dataset. Oral statin and bisphosphonate use was investigated as a risk factor for the development of MGUS/MM and MGUS progression using the UK CPRO dataset. While there was evidence of a reduced risk of MGUS/MM in association with oral statin use, an increased risk of both MGUS and MM was observed among oral bisphosphonate users most likely as a result of detection bias and/or reverse causality. Post-diagnostic statin use was also associated with a reduced risk of MGUS progression to any Iymphoproliferative disorder but not MM. Overall, the studies conducted as part of this thesis support a role for chronic antigenic stimulation in the development of MGUS and MM, and suggest a potential role for statins as chemopreventive agents within the MGUS/MM setting. Further research is however warranted to confirm these findings.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available