An investigation of the effect of hormonal medications, sex hormones, and inflammatory factors on cancer risk

  • Niamh Doherty

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Cancer is a global public health concern. The wide impact of cancer through premature death, increased burden on the health system and economy, and reduction in quality of life of survivors is a priority for public health. Furthermore, the burden of cancer is set to rise with increasing the growing elderly population. Understanding cancer aetiology and risk factors through cancer epidemiology is key to public health research and prevention. The overall aims of this thesis were to use large population-based databases to determine the risk of cancers, including kidney, bladder, colorectal, gastroesophageal, and melanoma, associated with several exposures relating to sex hormones and inflammatory factors.

A large male predominance in incidence is observed in many cancers. This has not been fully attributable to difference in risk factor profiles between the sexes. Therefore, it is hypothesised that the observed sex differences in cancer incidence could be driven by sex hormones. The commonly prescribed medication, 5-alpha reductase inhibitors, is used to treat men with benign prostatic hyperplasia by reducing the conversion of testosterone to its more potent form of dihydrotestosterone. Pre-clinical evidence has suggested a role for 5-alpha reductase inhibitors and cancer development but evidence to date has been conflicting regarding bladder cancer and there is a lack of evidence in relation to other cancer sites. This thesis investigated use of 5-alpha reductase inhibitors in association with kidney, bladder, colorectal, gastroesophageal, and melanoma skin cancers, when compared to use of alpha-blockers. This thesis found no associations between the use of 5-alpha reductase inhibitors and cancers of the kidney, bladder, colorectum, stomach or oesophagus. However, a higher risk of melanoma skin cancer was observed with 5-alpha reductase inhibitors. Additionally, circulating sex hormone levels and reproductive factors in association with kidney and bladder cancers were investigated.

Inflammation is an important part of the innate immune response. Research has indicated that inflammation, particularly chronic systemic inflammation, can mediate processes in early carcinogenesis. Pre-diagnostic levels of C- reactive protein, an acute phase protein in the systemic inflammatory cascade, have previously been linked to an increased risk of urinary tract cancers including kidney, bladder, renal pelvis, and ureter cancers. In addition, urinary stones, as an inflammatory condition directly effecting the kidney and bladder, have been linked to kidney, upper urinary tract cancers, and bladder cancer. This thesis investigated the risk of kidney and bladder cancers with pre-diagnostic levels of C-reactive protein and diagnosis of urinary stones. High C-reactive protein levels were associated with an increased risk of kidney cancer. Whereas prior diagnosis of urinary stones was associated with a substantial increased risk of renal pelvis and ureter cancer, but not kidney or bladder cancer.

In conclusion, research from this thesis has contributed to the knowledge base of 5ARi use with kidney, bladder, colorectal, gastroesophageal and melanoma skin cancers, in addition to evidence regarding hormonal exposures, CRP, and urinary stones with kidney and bladder cancer. Alongside other research this thesis will provide insights into cancer aetiology and future development of public health interventions.

Date of AwardJul 2024
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsNorthern Ireland Department for the Economy
SupervisorChristopher Cardwell (Supervisor) & Blánaid Hicks (Supervisor)

Keywords

  • cancer epidemiology
  • kidney cancer
  • bladder cancer
  • 5-alpha reductase inhibitors
  • hormones
  • inflammation

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