This study examined the association between statin use and cancer risk among the Korean population. We found a significant association between statin use for a duration of at least 6 months and a reduced risk of cancer and cancer mortality. Additionally, cancer mortality according to cumulative statin use (in cDDDs) was examined, and a dose-response relationship was confirmed with regard to all-cancer deaths, gastric cancer deaths, and colorectal cancer deaths.
Previous studies on statin use for cancer prevention have been mixed. Our results related to cancer incidence are similar to those of previous studies that found associations between statin use and significant decreases in the incidence of gastric cancer  and colorectal cancer . Additionally, this study’s results are consistent with those of another study that analyzed the effects of statin use on site-specific cancer risk and found that mortality was lower for colorectal cancer when statins had been prescribed before the diagnosis was made and that mortality was lower for esophageal cancer when patients took statins .
A meta-analysis of 11 studies on gastric cancer found a significant 32% decrease in cancer incidence among statin users. Another study found that statins had a preventative effect against stomach cancer. In addition, a recent meta-analysis of 42 studies on colorectal cancer found an association between statin use and an overall risk reduction of 10% for colorectal cancer . Another umbrella systematic review also found evidence that suggested that statins had a preventive effect against esophageal cancer .
In addition, this study’s results are consistent with those of a study that found lower mortality for colorectal cancer after analyzing the effects of pre-diagnosis statin use and a reduction in esophageal cancer mortality related to statin use . An umbrella meta-analysis of previous meta-analysis studies showed that statins reduced colorectal cancer mortality by 18% , and another meta-analysis of seven studies found a 20% reduction in cancer mortality related to statin use . Other studies distinguished between pre-diagnosis statin use and post-diagnosis statin use. A meta-analysis of 14 studies on colorectal cancer found an 18% reduction in mortality related to pre-diagnosis statin use and a 14% reduction in mortality related to post-diagnosis statin use . Other studies, however, have found an association between improved cancer mortality and pre-diagnosis statin use only [28, 30, 33]. Additionally, another meta-analysis of five studies found a 16% reduction in esophageal cancer mortality related to statin use 
One notable distinction in our study is our examination of potential dose-response relationships. In this study, we collected data on statin dosages and stratified subjects according to statin dosage. Despite the large number of studies that have examined the association between cancer incidence and statin use, relatively few studies have examined the effects of cumulative statin use on cancer incidence and mortality related to gastric, colorectal, and esophageal cancer. We classified cumulative statin use into the following three categories: less than 730 cDDDs, 730-1,459 cDDDs, or 1,460 cDDDs or more. Our results showed an association between cumulative statin use (in cDDDs) and a decreased risk of cancer and cancer mortality.
Previous studies have examined the dose-response relationship between statin use and other cancers. Studies have identified a dose-response relationship between 28-90 cDDDs, 91-65 cDDDs, and more than 365 cDDDs and a reduced risk of hepatocellular carcinoma compared to that of non-statin users [51, 52], However, a study in the US that surveyed participants about the duration for which they took statins—classified into less than 2 years, 3-6 years, and 6 years or more—found no statistically significant association between the duration of statin use and the risk of pancreatic cancer . Another study in Scotland that distinguished between participants who had taken 1-12 prescriptions and participants who had taken 12 prescriptions or more found no evidence of an association between statin use and breast cancer death in a dose-response analysis .
This study compared the outcomes of interest using a quasi-experimental design to analyze health insurance claims data. Data covering the total population of South Korea was used for analysis, and the findings can be generalized to other contexts due to the large amount of real-world data used for analysis; therefore, this study has several strengths. First, our study is highly representative since it is a cohort-based study of the entire general population of South Korea. There are few cohort studies that have covered more than 1 million people, and, to our knowledge, no study has investigated associations between statin use and the risk of cancer across the entire population. Second, our analysis of statin users among the general population is the first to assess the risk of cancer and cancer mortality simultaneously. We used data on individuals’ causes of death from Statistics Korea for our analysis of cancer mortality and its association with statin use. Third, we investigated the dose-response relationship between cancer risk and mortality and statin use, measured in cDDDs, which were calculated by multiplying daily dosages by the duration of statin use. This calculation is advantageous since it takes into account variable statin dosages and durations for which statins were taken. By classifying subjects according to the duration for which they took statins, their dosages, and their medication adherence, we quantified cancer risk by directly comparing subjects according to statin use in clinical practice. Fourth, we defined statin users as patients who took statins for at least 6 months in order to avoid bias resulting from short-term statin users being included in the analysis. In addition, we excluded patients who died or had new cancer diagnoses within 1 year during the follow-up period to eliminate the effects of other potential underlying diseases on the analysis.
However, there also are several limitations to the study. This is a retrospective study, so confounding factors related to disease progression that may have occurred were not recorded. Second, continued use of statins could potentially explain the reduced risk of death. For example, a poor prognosis might influence statin use, so when patients later stop taking statins as their disease progress worsens, it could potentially lead to disproportionately high mortality among statin users that is ultimately unrelated to their actual statin use. In addition, we used claims data and assumed that patients might take their prescribed medicines.
In conclusion, statin use is associated with a reduced risk of gastric, colorectal, and esophageal cancer incidence, as well as a lower risk of death from gastric cancer and colorectal cancer. However, further studies that are larger and multinational in scope are needed to confirm the beneficial effects of statins on survival for the three types of cancers examined in this study.