Association of Aspirin, Metformin, and Statin Use with Gastric Cancer Incidence and Mortality: A Nationwide Cohort Study

Abstract

Anticancer effects of aspirin, metformin, and statins against gastric cancer, one of the most common cancers in the world, have been reported. This retrospective cohort study aimed to investigate independent associations of aspirin, metformin, and statin use with gastric cancer incidence and mortality after adjustment for concomitant use of other drugs, using pooled cohort data extracted from the Korean National Health Insurance claim database. Follow-up started on January 1, 2004 and ended at the date of gastric cancer diagnosis, death, or December 31, 2013. Exposures to drugs were defined as cumulative duration of use for aspirin and cumulative defined daily dose for metformin and statin, and were entered as time-dependent variables in Cox analysis models to avoid immortal time bias. Use of aspirin for longer than 182.5 and 547.5 days during 2-year interval was associated with reduced risks of gastric cancer incidence and mortality, respectively. Patients with diabetes were at higher risk of gastric cancer incidence and mortality than nondiabetic people, regardless of metformin treatment. However, metformin use among patients with diabetes was associated with a reduction in gastric cancer mortality in a dose-response manner. Statin use was also associated with a reduction of gastric cancer mortality in the general population, but not with gastric cancer incidence. In conclusion, long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population, but metformin or statin use was only associated with a reduction of gastric cancer mortality in patients with diabetes and in the general population, respectively. Prevention Relevance: Long-term use of aspirin was independently associated with reduced incidence and mortality of gastric cancer in the general population. Metformin or statin use, however, was only associated with a reduction of gastric cancer mortality in diabetic patients and in the general population in a dose-response manner, respectively.

Statins: a repurposed drug to fight cancer

“…However, the results of a population-based epidemiologic study showed that the use of statins was not associated with overall prostate cancer risk [67], although the credibility of the results of the study are open to question due to the relatively small sample size and the existence of potential selection and recall biases. In gastric cancer, a recent nationwide cohort study suggested that the use of statins is related to a decrease in gastric cancer mortality in the general population, but has no correlation with the incidence of gastric cancer [30]. A recent prospective observational study of ovarian cancer patients conducted in Australia suggested that the increase in patient survival is related to the use of lipophilic statins, but not to hydrophilic statins [59].…”

Association of Common Medications and the Risk of Early-Onset Gastric Cancer: A Population-Based Matched Study

“…Other commonly prescribed medications have been proposed as possibly chemopreventive for gastric cancer development, including statins, NSAIDs, metformin, and COX-2 inhibitors [ 11 – 14 ]. However, existing studies have not yet specifically examined the potential protective role of these medications in EOGC.…”

“…Other frequently prescribed medications, including statins (HMG-CoA reductase inhibitors), metformin, nonsteroidal anti-inflammatory medications (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors, have also been associated with a potentially reduced risk of gastric cancer development [ 11 – 13 ]. Statin medications have been proposed to have antiangiogenic, immunomodulatory, and proapoptotic properties based on in vitro studies in mice and human gastric cancer cell lines, as well as in retrospective studies [ 14 , 15 ].…”

“…Statin medications have been proposed to have antiangiogenic, immunomodulatory, and proapoptotic properties based on in vitro studies in mice and human gastric cancer cell lines, as well as in retrospective studies [ 14 , 15 ]. Metformin has been proposed to have a potential protective effect against gastric cancer; however, data are mixed, as some observational studies have demonstrated no significant reduction in gastric cancer risk associated with metformin [ 11 , 16 , 17 ]. NSAIDs and COX-2 inhibitors both exert anti-inflammatory effects thought to potentially protect against gastric carcinogenesis [ 12 , 18 ].…”

Statins’ Regulation of the Virulence Factors of Helicobacter pylori and the Production of ROS May Inhibit the Development of Gastric Cancer

“…The association between statin use and lower GC risk remains elusive, and some discrepancies have emerged. A study by Cho et al showed that statins were able to reduce mortality in GC but failed to decrease its incidence [ 98 ]. These findings are inconsistent with results from previous systematic reviews and meta-analyses, which may be because different study populations and settings were analyzed [ 17 ].…”