Use of Hypolipidemic Drugs and the Risk of Second Primary Malignancy in Colorectal Cancer Patients

Abstract

An increasing number of studies has brought evidence of the protective role of statin use against different types of cancer. However, data on their association with second primary malignancies (SPMs) are lacking. The purpose of this study was to determine the role of hypolipidemic treatment in the prevention of second primary cancer in colorectal cancer (CRC) survivors. We conducted a retrospective single-institution study of 1401 patients with newly diagnosed colorectal cancer from January 2003 to December 2016, with follow-up until December 2020. An SPM was detected in 301 patients (21%), and the incidence was significantly lower in patients with statin medication. However, stratification by cancer types revealed an increased incidence of bladder and gastric cancer in hypolipidemic users. A Kaplan−Meier analysis of early-stage CRC survivors with an SPM showed a significant survival benefit in patients without a history of hypolipidemic treatment. Despite the protective role of statins on overall second cancer incidence, these data indicate that CRC survivors treated with hypolipidemic drugs should be screened more cautiously for SPMs, especially for gastric and bladder cancer.

The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis

“…19), short-term users (RR: 1.10, 95% CI 0.93-1.31), or long-term users (RR: 0.98, 95% CI 0.81-1.20), and these were reported to be not statistically significant (p-values not reported). The increased risk reported in the study by Farwell et al [37] was not statistically significant (univariate HR: 0.94, 95% CI 0.80-1.11, multivariate HR: 0.94, 95% CI 0.77-1.13, p-trend = 0.25), and in the study by Halámková et al [42], although the percentage of patients with UBC was higher on the user group (3.6% vs. 11.3%, or 11/304 vs. 6/53, p = 0.015, compared to a population reference of 2.9%), important factors such as smoking and obesity were not addressed.…”

“…Regarding the UBC risk on statin patients, we performed a meta-analysis of four RCTs [27][28][29][30] and six cohort [36,37,[39][40][41][42] studies (Supplementary Table S3). The included population consisted of 13,932 statin users and 13,917 controls for the RCTs analysis, and 544,862 users and 621,806 controls for the cohort studies.…”

“…Of them, 4 were RCTs, 6 were case-control studies and 22 were cohort reports. Reports that examined and reported UBC incidence included four RCTs [27][28][29][30], five case-control studies [31][32][33][34][35], and seven cohort [36][37][38][39][40][41][42] studies. Eight cohort [14,[43][44][45][46][47][48] studies reported information on local control and recurrence.…”

“…UBC incidence was the primary outcome of this systematic review and meta-analysis. Reports that examined and reported UBC incidence included four RCTs [27][28][29][30], five case-control studies [31][32][33][34][35], and seven cohort studies [36][37][38][39][40][41][42].…”

Fibrates Affect Levels of Phosphorylated p38 in Intestinal Cells in a Differentiation-Dependent Manner

“…A recent review of the role of hypolipidaemic treatment in the prevention of second primary cancers in colorectal cancer survivors showed that fibrates did not have a significant chemoprotective effect against cancer. However, the authors note that the subgroup of patients treated with fibrates in their study was too small [23].…”