Individual and joint use of statins and low‐dose aspirin and risk of colorectal cancer: A population‐based case–control study

Abstract

Recent research has drawn attention to protective effects of statins on colorectal cancer (CRC) and possible joint effects with other drugs. Because statins are often administered in combination with low-dose aspirin for the prevention of cardiovascular disease, the aim of our study was to investigate individual and combined effects of statins and low-dose aspirin on CRC risk. We assessed use of statins and low-dose aspirin in 540 cases with histologically confirmed incident CRC and 614 control subjects in a populationbased case-control study in Germany. Multiple logistic regression was used to estimate the impact of regular use of either low-dose aspirin or statins, and of both drugs combined on CRC risk. We found modest risk reduction of CRC for regular use of low-dose aspirin (adjusted odds ratio 0.77, 95% confidence interval 0.55-1.07) and a stronger association with regular use of statins (OR 0.65, 95% CI 0.43-0.99) or use of both drugs (OR 0.63, 95% CI 0.36-1.10). Combined use of low-dose aspirin and statins was associated with risk reduction by 62% after 5 or more years (OR 0.38, 95% CI 0.15-0.97). Combinational chemoprevention with lowdose aspirin and statins might provide stronger risk reduction than either of the single drugs after at least 5 years use, but confirmation is needed, preferably in prospective cohort studies and eventually by randomized controlled trials. ' 2007 Wiley-Liss, Inc.Key words: chemoprevention; colorectal cancer; aspirin; statins; risk Recent research has drawn attention to risk reduction of colorectal cancer (CRC) with the use of statins, 1-9 and a number of epidemiological studies have suggested that nonsteroidal antiinflammatory drugs (NSAIDs) 10-18 may reduce the risk of CRC. However, evidence remains limited, especially for low-dose aspirin, 12,16,[19][20][21][22] and not confirmed by randomized controlled trials (RCTs) so far. [23][24][25][26][27] It has been suggested that NSAIDs and statins in combination might provide stronger risk reduction of CRC than single drug treatment, 28-30 but knowledge about possible interaction of both types of drugs remains limited. 7,31 Because statins and low-dose aspirin are used for cardiovascular disease (CVD) prevention by many older adults, and because both drugs are often administered in combination, their individual and joint use might have a large impact on CRC risk. We aimed to assess this impact in a large population-based case-control study from Germany. Methods Study design and study populationThis population-based case-control study was conducted in the Rhine-Neckar-Odenwald region in the South-West of Germany. Details of the study design have been reported elsewhere. 32 Briefly, patients were included if invasive, histologically confirmed CRC (ICD 10 pos. C18-C20) was diagnosed for the first time between January 2003 and June 2004. All 22 hospitals in the study region treating patients with CRC agreed to participate in the study. Control individuals were randomly selected from lists of population registries and frequency-matc...

Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: A Danish cohort study

“…Cohort subjects were followed for a primary diagnosis of CRC from enrollment until the earliest of the following events: date of diagnosis of cancer (except non-melanoma skin cancer), date of death, date of emigration, or 30 [43].…”

“…A recent post-trial analysis has suggested that the chemopreventive effect of NSAIDs on colorectal neoplasia may vary by body mass index (BMI) as marker for obesity [27]; however, the epidemiologic data on the influence of BMI are conflicting [19,21]. There is also some evidence that the chemopreventive effect of NSAIDs may be increased by use of statins [28][29][30][31], although the cumulative epidemiologic evidence to date does not point to a material reduction in CRC risk with statin use [32].…”

Combination regimen with statins and NSAIDs: A promising strategy for cancer chemoprevention

“…51 In a population-based case-control study, the effects of statins and aspirin were evaluated on the risk of colorectal cancer. 52 Overall, 537 patients with histologically confirmed incident colorectal cancer and 612 control individuals were included in the study. Regular use of low-dose aspirin (94% of doses used were 100 mg) was associated with modest risk reduction on colorectal cancer (adjusted OR 5 0.77, 95% CI 5 0.55-1.07), while a stronger risk reduction was found associated with regular use of statins, mostly atorvastatin and simvastatin (OR 5 0.65, 95% CI 5 0.43-0.99).…”

Risk of Proximal Colonic Neoplasms in Asymptomatic Adults Older Than 50 Years Found to Have Distal Hyperplastic Polyps on Routine Colorectal Cancer Screening

“…With the exception of the latter two variables, these factors too have been documented by other researchers to be associated with neoplasms in the large intestine. [21][22][23][24][25][26][27][28][29] What was unique to this particular study was the identification of potentially two new risk factors for proximal neoplasms within the asymptomatic screening population (use of estrogen and a history of cancer other than CRC). Although it would have been both provocative and insightful to be able to compare and contrast the outcomes of this investigation with the outcomes of others mentioned in this article, this was not realistically feasible because of diverse study designs, inclusion and exclusion criteria, operational definitions for the distal colon, applications of multivariate and statistical techniques, sample sizes, baseline demographic characteristics, and control or reference groups.…”