Title:
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Prior medical history, drug exposure and risk of multiple myeloma
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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.
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