Higher Prevalence of Prior Prostate Cancer in Patients Diagnosed with Chronic Myelogenous Leukemia.
Authors: Assouline Sarit , Delaney J.A. , Gambacorti Carlo , Suissa Samy 
Published: April 2020

If defective DNA repair mechanisms result in the development of the Philadelphia chromosome and chronic myelogenous leukemia (CML), then individuals with CML are at higher risk in general to develop genetic mutations. These mutations can then result in other cancers. A retrospective review of patients treated with interferon and then imatinib for CML did not demonstrate an overall increased risk of cancer, but did report a 4-fold increased incidence of prostate cancer among men receiving imatinib compared with the general population1. The increased risk of prostate cancer might be associated with the use of imatinib. Alternatively, it may be due to a predisposition to prostate cancer among men with CML.

Using the United Kingdom’s General Practice Research Database (GPRD) we conducted a nested case-control study to examine whether men with CML have a higher prevalence of prostate cancer compared to men without CML. The GPRD contains extensive clinical information on a population of approximately 3.5 million patients, about 5% of the UK population. The collected data include demographics, medical diagnoses, prescriptions, referrals to hospitals, lifestyle variables, hospital discharge reports, as well as patient care information2.

One-hundred ninety seven males with CML were identified in the database from 1995 to 2005. Of these, 12 were excluded because they had not participated in the database for at least 180 days, no controls could be found, or the medical history was inadequate. For the remaining 185 patients, 1844 controls were matched for age, general practice attended, and the year of start in the practice.

In total, 8 cases and 52 controls had a history of prostate cancer. The mean age among the cases was 63.2 years (range 18 to 89 years); the mean age among the controls was 63.1 years (range 8 to 97 years).

In a conditional logistic regression model, the relative risk of having been previously diagnosed with prostate cancer among patients with CML was 2.65 (95% confidence interval 1.18 to 5.94, p=0.018).

The mean time between prostate cancer diagnosis and first diagnosis of CML was 1033.5 days (range 61 to 2996 days). The mean time from the diagnosis of prostate cancer and identification as a control was 1391 days (range 2 to 2951 days). These times and ranges are not disparate enough to suggest that an ascertainment bias could account for a higher incidence of CML among patients with prostate cancer.

Thus, the relative risk of developing CML is higher among patients with a prior diagnosis of prostate cancer, and factors inherent to the host may predispose them to develop prostate cancer and CML. Furthermore, this study provides support for the theory that either exposure to imatinib may not predispose to second malignancy at all, or that the oncogenic effect of imatinib may be augmented by a pre-existing risk for second malignancy among these patients because the prostate cancer predated the diagnosis of CML.

This database will also be used to determine whether the association between CML and prostate cancer can be extended to CML and other cancers. The data presented here will allow for a greater understanding of any future prospective studies examining the association between exposure to imatinib and the development of prostate cancer and other malignancies.