Inverse Association between Statin Use and Stomach Cancer Incidence in Individuals with Hypercholesterolemia, from the 2002–2015 NHIS-HEALS Data

Abstract

Purpose: To investigate the association between statin use and stomach cancer incidence in individuals with hypercholesterolemia. Materials and methods: To examine the cumulative effect of statins, we defined a statin user as one who used statins during 2002–2003 at baseline. Statin users were further classified into high and low users according to the medication possession rate. Statin non-users consisted of participants who had never used statins during the entire period of 2002–2015, despite having hypercholesterolemia (total cholesterol level ≥250 mg/dL at baseline). Ultimately, 17,737 statin users and 13,412 statin non-users were used in the analysis. We performed survival analyses, considering the diagnosis of stomach cancer as an event of interest. Results: Median follow-up duration was 12.9 years. The cumulative incidence rates of stomach cancer were lowest in high users (1.90% in men and 0.98% in women). Compared to non-users, hazard ratios (95% confidential intervals) for stomach cancer of low users and high users were 0.953 (0.755–1.203) and 0.526 (0.399–0.693) in men and 0.629 (0.457–0.865) and 0.370 (0.256–0.535) in women, respectively, after adjusting for possible confounders. Conclusions: We observed an inverse association between statin use and stomach cancer incidence in participants with hypercholesterolemia.

Influence of cholesterol on cancer progression and therapy

“… [206] 45 Gastric Simvastatin in vitro & Clinical AGS, ATCC CRL 1739 cells Statin reduces the incidence of gastric cancer by attenuating Helicobacter pylori CagA translocation [202] 46 Stomach Statin Clinical 17,737 statin users and 13,412 statin non-user The use of statin decreases the incidence of stomach cancer on hypercholesterolemic individuals. [252] 47 Blood (chronic myelogenous leukemia) Avasimibe, Imatinib in vitro & in vivo K562R (imatinib-resistant) Avasimibe sensitized K562R to imatinib [226] 48 Blood (lymphoblasts and myeloma cells) Lovastatin Simvastatin Cerivastatin Leverkusen, Atorvastatin in vitro Jurkat, CEM, IM9, U266 cell MCC-2 Statin induces mitochondrial apoptosis pathway in human T, B, and myeloma tumor cells causing cell death [200] 49 Blood (leukemia and lymphoma) Simvastatin, Atorvastatin, Rosuvastatin, Fluvastatin,Venetoclax in vitro, in vivo , & Clinical AML cells (OCI-AML2, OCI-AML3, MOLM13), DLBCL cells (OCI-LY8, SU-DHL4).C57BL/6 N mice Statin increases the pro-apoptotic activity of Venetoclax (B cell lymphoma-2 inhibitor) in primary leukemia and lymphoma cells [253]

Fig. 6 Schematic representation of cholesterol associated changes in cancer cells and available therapeutic targets.

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Incidence Hypertension and Fasting Blood Glucose from Real-World Data: Retrospective Cohort for 7-Years Follow-Up

“…The National Health Insurance Service-National Health Screening (NHIS-HEALS) database includes medical diagnoses, drug prescriptions, demographic characteristics, and information from health examinations, such as self-administered health surveys, physical examinations, and biochemical test results. Details of the cohort have been published previously [ 20 , 21 , 22 , 23 ].…”

Association between Statin Use and Gastric Cancer: A Nested Case-Control Study Using a National Health Screening Cohort in Korea

“…Due to the high hepatic washout selectivity of hydrophilic statins and the high penetration ability into the cell plasma membrane of lipophilic statins, lipophilic statins may be effective in nonhepatic, nonintestinal, solid organ cancers, including breast and ovary cancers [11][12][13]. Nevertheless, statins have drawn attention for their potential anticancer effects in gastric cancers among Asian countries with a high prevalence of gastric cancers [14][15][16][17][18]. In vitro evidence indicates the anticancer activity of statins in gastric cancers, primarily by means of downregulation of the mevalonate pathway, which is critical for vital cellular functions maintaining membrane integrity and cell cycle progression [5,6,[18][19][20].…”

“…Population-based studies and meta-analyses have supported the reduced gastric cancer risk in individuals who had received statins [17,22,23]. There are two nationwide epidemiological studies regarding the influence of prior statin use on the development of stomach cancers based on Korean individuals [16,24]. These studies did not specifically investigate the relationships of the duration of statin use or statin types with the incidence and mortality of gastric cancer, and whether prior statin use affects the risk or mortality of gastric cancer according to the statin types and duration of use remains debated.…”