Statin use and the risk of colorectal cancer in a population-based electronic health records study

Ibáñez‐Sanz, Gemma; Guinó, Elisabet; Pontes, Caridad; Quijada-Manuitt, MÂa Ángeles; Peña-Negro, Luisa C de la; Aragón, María; Domínguez, Marga; Rodríguez‐Alonso, Lorena; Blasco, Alex; García-Rodríguez, Ana; Morros, Rosa

doi:10.1038/s41598-019-49877-5

Cited by 23 publications

(18 citation statements)

References 39 publications

(42 reference statements)

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“…Conversely, a recent case-control study performed in Catalonia showed no significant decrease of CRC risk associated to any statin exposure. When stratification was performed by cancer site, reduction of rectal cancer risk was seen in statin users (OR: 0.87, 95% CI: 0.81–0.92) [ 107 ]. Overall, the role of statins in relation to the incidence of CRC seems to be still controversial and, to date as data suggest, only a weak action as a chemopreventive agent [ 108 ].…”

Section: Resultsmentioning

confidence: 99%

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Cantini

Giglio

Bittoni

et al. 2020

Cancers

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Colorectal cancer is characterized by high incidence worldwide. Despite increased awareness and early diagnosis thanks to screening programmes, mortality remains high, particularly for patients with metastatic involvement. Immune checkpoint inhibitors or poly (ADP-ribose) polymerase (PARP)-inhibitors have met with disappointing results when used in this setting, opposed to other malignancies. New drugs with different mechanisms of action are needed in this disease. Drug repurposing might offer new therapeutic options, as patients with metastatic colorectal cancer often share risk factors for other chronic diseases and thus frequently are on incidental therapy with these drugs. The aim of this review is to summarise the published results of the activity of drugs used to treat chronic medications in patients affected by colorectal cancer. We focused on antihypertensive drugs, Non-Steroid Anti-inflammatory Drugs (NSAIDs), metformin, antidepressants, statins and antibacterial antibiotics. Our review shows that there are promising results with beta blockers, statins and metformin, whereas data concerning antidepressants and antibacterial antibiotics seem to show a potentially harmful effect. It is hoped that further prospective trials that take into account the role of these drugs as anticancer medications are conducted.

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Section: Resultsmentioning

confidence: 99%

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Cantini

Giglio

Bittoni

et al. 2020

Cancers

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“…MVA biosynthetic pathway is considered a potential drug target to improve therapeutic window in cancer ( 11 ) ( Figure 4 ). However, despite mounting body of preclinical and epidemiological evidences suggesting MVA pathway inhibitors (i.e., statins) as anticancer agents, many patients remained non-responsive to drug treatment in some cancer clinical trials ( 13 , 20 , 23 , 30 , 33 , 186 ). This is, in part, because cancer cell selectivity, as well as predictive biomarkers of drug efficacy and drug resistance, is still poorly understood.…”

Section: Efficacy and Resistance To Mva Pathway Inhibitors In Human Tmentioning

confidence: 99%

“…Despite clinical evidences supporting the use of MVA pathway inhibitors (i.e., statins) for limiting cancer morbimortality are relatively low, increasing preclinical (11)(12)(13)(14)(15)(16)(17)(18)(19) and epidemiological (20)(21)(22)(23)(24)(25)(26)(27)(28) studies sustain the inverse association between statins and cancer-specific mortality rate. This beneficial effects of statins have been described in several types of cancer, including osteosarsocoma/chondrosarcoma (16)(17)(18), prostate (24,26), colon (29,30), breast (19,31), liver (32,33), pancreas (34), ovarian (35,36), esophageal (37,38), lung (39), and hematological malignances (40). Interestingly, statins may suppress epithelialmesenchymal transition (EMT) program together with the inhibition of cancer stem cell generation, maintenance, and expansion (6,41).…”

Section: Introductionmentioning

confidence: 97%

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

et al. 2021

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A hallmark of cancer cells includes a metabolic reprograming that provides energy, the essential building blocks, and signaling required to maintain survival, rapid growth, metastasis, and drug resistance of many cancers. The influence of tumor microenviroment on cancer cells also results an essential driving force for cancer progression and drug resistance. Lipid-related enzymes, lipid-derived metabolites and/or signaling pathways linked to critical regulators of lipid metabolism can influence gene expression and chromatin remodeling, cellular differentiation, stress response pathways, or tumor microenviroment, and, collectively, drive tumor development. Reprograming of lipid metabolism includes a deregulated activity of mevalonate (MVA)/cholesterol biosynthetic pathway in specific cancer cells which, in comparison with normal cell counterparts, are dependent of the continuous availability of MVA/cholesterol-derived metabolites (i.e., sterols and non-sterol intermediates) for tumor development. Accordingly, there are increasing amount of data, from preclinical and epidemiological studies, that support an inverse association between the use of statins, potent inhibitors of MVA biosynthetic pathway, and mortality rate in specific cancers (e.g., colon, prostate, liver, breast, hematological malignances). In contrast, despite the tolerance and therapeutic efficacy shown by statins in cardiovascular disease, cancer treatment demands the use of relatively high doses of single statins for a prolonged period, thereby limiting this therapeutic strategy due to adverse effects. Clinically relevant, synergistic effects of tolerable doses of statins with conventional chemotherapy might enhance efficacy with lower doses of each drug and, probably, reduce adverse effects and resistance. In spite of that, clinical trials to identify combinatory therapies that improve therapeutic window are still a challenge. In the present review, we revisit molecular evidences showing that deregulated activity of MVA biosynthetic pathway has an essential role in oncogenesis and drug resistance, and the potential use of MVA pathway inhibitors to improve therapeutic window in cancer.

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“…25). Study design has already been published (26,27). Briefly, SIDIAP database comprises clinical information routinely collected by primary care professionals, hospital admissions, and dispensed prescriptions since 2005.…”

Section: Data Sourcementioning

confidence: 99%

Chondroitin Sulphate and Glucosamine Use Depend on Nonsteroidal Anti-inflammatory Drug Use to Modify the Risk for Colorectal Cancer

Ibáñez‐Sanz

Guinó

Morros

et al. 2020

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: A safe and effective colorectal cancer chemoprevention agent remains to be discovered. There is little evidence regarding the protective effect of chondroitin sulphate and glucosamine on colorectal cancer. We aimed to assess the association between colorectal cancer risk and the use of chondroitin sulphate and glucosamine using a large cohort with dispensed data.Methods: We performed a population-based case-control study in Catalonia using primary care reimbursed medication records (SIDIAP database). The study included 25,811 cases with an incident diagnosis of colorectal cancer and 129,117 matched controls between 2010 and 2015.Results: The prevalence of ever use was 9.0% (n ¼ 13,878) for chondroitin sulphate, 7.3% (n ¼ 11,374) for glucosamine, and 35% for regular use of nonsteroidal anti-inflammatory drugs (NSAID; n ¼ 45,774). A decreased risk of colorectal cancer was observed among chondroitin sulphate use [OR: 0.96; 95% confidence interval (CI), 0.91-1.01], glucosamine use (OR: 0.92; 95% CI, 0.87-0.97), and concurrent use of chondroitin sulphate and glucosamine (OR: 0.83; 95% CI, 0.70-0.98). Especially for glucosamine, there was a dose-response association regarding duration and cumulative dose. The analysis stratified by simultaneous use with other NSAIDs showed that these drugs used without other NSAIDs do not reduce risk (OR: 1.06; 95% CI, 0.74-1.51). However, they may have a synergistic protective effect when used with other NSAIDs (OR: 0.80; 95% CI, 0.72-0.88).Conclusions: This study does not provide strong support for an independent protective association of chondroitin sulphate or glucosamine on colorectal cancer risk in our population. However, these drugs may have a synergistic beneficial effect among NSAID users.Impact: Chondroitin sulphate or glucosamine may contribute to the protective effect of NSAID use in colorectal cancer.

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Statin use and the risk of colorectal cancer in a population-based electronic health records study

Cited by 23 publications

References 39 publications

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

The Mevalonate Pathway, a Metabolic Target in Cancer Therapy

Chondroitin Sulphate and Glucosamine Use Depend on Nonsteroidal Anti-inflammatory Drug Use to Modify the Risk for Colorectal Cancer

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