Pharmacoepidemiological studies of breast and colorectal cancer: The association between statins and cancer outcomes
Citation:SMITH, AMELIA, Pharmacoepidemiological studies of breast and colorectal cancer: The association between statins and cancer outcomes, Trinity College Dublin.School of Medicine, 2019
Full thesis - Final Hardbound_Amelia Smith2019.pdf (PhD Thesis, examined and approved) 4.873Mb
Breast and colorectal cancer are two of the most commonly diagnosed cancers in Ireland and worldwide, and a significant cause of cancer deaths. Statins, which are drugs that are commonly used in the prevention of cardiovascular disease, have been identified as having a potential role in the treatment of these cancers. Pre-clinical, clinical, and epidemiological studies have highlighted these potential pleiotropic effects of statins; however, results are conflicting and research is on-going. Pharmacoepidemiological studies provide the opportunity to investigate the effects of drug exposures on breast and colorectal cancer outcomes using existing datasets. Records from the National Cancer Registry Ireland, which have been linked to prescription claims data from the Health Service Executive Primary Care Reimbursement Service, for patients diagnosed with breast or colorectal cancer between 2001 and 2011, were used in this thesis. Analyses of the patterns of statin use in the time prior to death from breast or colorectal cancer showed that the probability of continuing statin use was significantly lower in the three to six months prior to death from these cancers. These results suggest that it is important to account for peri-mortality changes in statin exposure in pharmacoepidemiological studies, to minimise potential reverse causation bias. In analyses of de-novo statin use and breast cancer-specific mortality, no association was found between de-novo statin initiation and breast cancer-specific mortality, after adjusting for important covariates (HR 0.88, 95% CI 0.66, 1.17). Subgroup analyses also yielded null associations. Analyses of de-novo statin use on colorectal cancer-specific mortality also found no significant association in multivariate adjusted analyses (HR 0.96, 95% CI 0.78, 1.19). These studies suggest there may be limited benefit for statins in an adjuvant setting for an unselected population. While no significant association was found between pre-diagnostic statin use and lymph node status at breast cancer diagnosis, pre-diagnostic statin use was associated with a significant, 19% reduction in breast cancer-specific mortality (HR 0.81, 95% CI 0.68, 0.96). Pre-diagnostic statin use was associated with a more marked, statistically significant, 31% reduction in breast cancer-specific mortality in patients with ER+ tumours (HR 0.69, 95% CI 0.55, 0.85). Finally, in analyses of pre-diagnostic statin use and lymph node status in colorectal cancer, no association was found in multivariate adjusted analyses. However, pre-diagnostic statin use was associated with a non-significant, 14% reduction in colorectal cancer-specific mortality (HR 0.86, 95% CI 0.73, 1.00). In analyses stratified by type of statin received, colorectal cancer survival benefit was significant in those who received a lipophilic statin (HR 0.75, 95% CI 0.61, 0.93) but not a hydrophilic statin. Strengths of these studies include the use of high-quality national-level cancer data, which is linked to detailed statin exposure data, enabling the robust study of the exposure-outcome relationship. However, the data used in these studies is a subset of the general population, defined by eligibility for General Medical Services scheme who are generally older and of lower socioeconomic status. The results from these studies are broadly consistent with previous research on associations between statins and breast and colorectal cancer. These studies contribute novel data on the importance of considering peri-mortality changes in statin exposure, and on the associations between pre and post-diagnostic statin exposure and breast and colorectal cancer outcomes. This is important due to the high prevalence of statin use in Ireland and worldwide, and the growing investigation of the effects of commonly used medications and cancer outcomes.
Author: SMITH, AMELIA
Publisher:Trinity College Dublin. School of Medicine. Discipline of Pharmacology & Therapeutics
Type of material:Thesis
Availability:Full text available