Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer

Spence, Andrew; Busby, John; Johnston, Brian T.; Baron, John A.; Hughes, Carmel; Coleman, Helen; Cardwell, Christopher

doi:10.1053/j.gastro.2017.10.044

Cited by 34 publications

(26 citation statements)

References 34 publications

(44 reference statements)

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“…The data sources have previously been described in full . Briefly, English cohort data were obtained from the UK Clinical Practice Research Datalink (CPRD), linked with the Office for National Statistics (ONS) and cancer registry information from the National Cancer Data Repository (NCDR).…”

Section: Methodsmentioning

confidence: 99%

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Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Spence

Busby

Hughes

et al. 2018

Pharmacoepidemiology and Drug

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Purpose Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population‐based gastric cancer cohorts. Methods Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time‐dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer‐specific mortality by statin use in multivariate analysis. Meta‐analysis techniques pooled results across the cohorts. Results The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer‐specific deaths. Statin use after diagnosis was associated with reduced cancer‐specific mortality (adjusted HR 0.83; 95% CI, 0.74‐0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73‐0.94 and adjusted HR 0.83; 95% CI, 0.64‐1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer‐specific mortality (adjusted HR 0.91; 95% CI, 0.84‐0.98). Conclusions In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer‐specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage.

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Section: Methodsmentioning

confidence: 99%

“…The data sources have previously been described in full. 18 Registry records in Scotland), apart from nonmelanoma skin cancer and in-situ tumours, were excluded from the cohort. 19 Patients with duplicate cancer registry records were also removed.…”

Section: Methodsmentioning

confidence: 99%

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Spence

Busby

Hughes

et al. 2018

Pharmacoepidemiology and Drug

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“…At this point, it should be noted that a few studies have been reported which did not find associations between aspirin or NSAID use and lower cancer mortality [121,129,130] and in some cases, they have been associated with even greater mortality [131] . Importantly, considerable caution and care must be taken with such studies where patients may be using the NSAIDs to offset pain in the terminal phases of cancers.…”

Section: Enhanced Clinical Outcomes From Using Nsaids Combined With Cmentioning

confidence: 93%

NSAID celecoxib: a potent mitochondrial pro-oxidant cytotoxic agent sensitizing metastatic cancers and cancer stem cells to chemotherapy

Ralph¹,

Nozuhur²,

Moreno‐Sánchez³

et al. 2018

JCMT

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Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phosphorylation (OxPhos) and increases mitochondrial production of reactive oxygen species (ROS). In primary tumors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer cells. Tumor reprogramming is initiated by activating nuclear respiratory factors and hypoxiainducible factors in response to changes in oxygen and ROS levels. Hence, hypoxia-induced pro-oxidative stress drives invasion and metastasis. However, it is also the Achilles' heel of metastatic cancer cells because pro-oxidative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis, whereas antioxidant agents promote their survival and tumor progression. Herein lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death, including metastatic cancer cells and cancer stem cells. This review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.

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“…The predominant adverse event caused by aspirin is GI bleeding, and there appears to be no valid evidence that the overall frequency of fatal GI bleeding is increased by daily low-dose aspirin [36,57,58]. On the other hand, recent populationbased study from the United Kingdom showed that lowdose aspirin was not associated with increased survival of patients diagnosed with esophageal or gastric cancer [59]. Thus, future studies would be of great interest to assess the exact effect of aspirin in the overall cancer incidence and mortality.…”

Section: Chemopreventionmentioning

confidence: 99%

General Aspects of Primary Cancer Prevention

Krstić

Mijač

Popović

et al. 2019

Dig Dis

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Background: Cancer is the second leading cause of death worldwide next to cardiovascular diseases. Despite the advancement in screening, early diagnosis, and development in treatment technology in last several decades, cancer incidence overall, particularly that of gastrointestinal (GI) cancers, is far from being controlled, and is expected to increase worldwide. Summary: Although numerous preclinical and population-based clinical studies have already made important progress in restraining the overall cancer incidence and mortality, the full potential of preventive strategy is still far from being realized, and remains at an early stage. There are several major challenges regarding this issue, and one of the crucial challenges is to maintain the balance between risks and benefits. As a result of past investments, primary prevention nowadays include the integration of various activities such as lifestyle changes to reduce risk, screening to detect early lesions, vaccines and preventive therapies aimed to actively interrupt the carcinogenic pathway. Long-term aspirin use seems to have the largest potential effect on the general population on cancer incidence and mortality overall, especially GI cancers. Helicobacter pylori eradication reduces the risk for gastric cancer and is advocated regardless of the symptoms and stage of disease. Metformin and statins are promising in cancer prevention in patients with type 2 diabetes. Vitamin D supplementation is promising in the prevention of colorectal adenoma recurrence. Key Message: However, additional studies are warranted to establish the potential of various agents and to identify more specific and highly targeted new agents for chemoprevention in digestive oncology.

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Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer

Abstract: In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Cited by 34 publications

References 34 publications

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

Statin use and survival in patients with gastric cancer in two independent population‐based cohorts

NSAID celecoxib: a potent mitochondrial pro-oxidant cytotoxic agent sensitizing metastatic cancers and cancer stem cells to chemotherapy

General Aspects of Primary Cancer Prevention

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