Cumulative Dose Threshold for the Chemopreventive Effect of Aspirin Against Gastric Cancer

Kim, Min-hyung; Chang, Jooyoung; Kim, Warrick Junsuk; Banerjee, Samprit; Park, Sang Min

doi:10.1038/s41395-018-0097-5

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…Regarding GC, the evidence on the role of aspirin on prevention has been more limited and there is no current recommendation as a chemopreventive agent. Consistent with previous evidence, however, a recent meta-analysis (Huang et al 2017) and a longitudinal study covering the whole population of South Korea concluded that long-term aspirin use was associated with reduction in GC risk (Kim et al 2018). In this high GC risk population, the protective effect was significant in those individuals with cumulative aspirin daily dose use for at least three years.…”

Section: Anti-cancer Strategies Targeting the Pro-inflammatory Mediatsupporting

confidence: 57%

“…Although most cancer research has focused on the molecular changes of the neoplastic cells, it is now recognized that non-tumoral cells in the tumor microenvironment, especially immune cells, proliferate with the tumor and provide essential support for its growth and invasion. The recognized protective effect of non-steroidal anti-inflammatory drugs against GC and other gastrointestinal tumors (Abnet et al 2009; Epplein et al 2008; Kim et al 2018) supports the role of chronic inflammation in carcinogenesis.…”

Section: Introductionmentioning

confidence: 84%

“…In this high GC risk population, the protective effect was significant in those individuals with cumulative aspirin daily dose use for at least three years. The evidence on the use of non-aspirin NSAIDs has shown less consistent results in protection against GC across studies (Kim et al 2018; Abnet et al 2009; Epplein et al 2009; Huang et al 2017). A recent study aimed to evaluate the protective effects of low-dose aspirin use after GC diagnosis found no association with GC-specific mortality after one year of follow-up (Spence et al 2018).…”

Section: Anti-cancer Strategies Targeting the Pro-inflammatory Mediatmentioning

confidence: 98%

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Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy

Piazuelo

Riechelmann

Wilson

et al. 2019

Current Topics in Microbiology and Immunology

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The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in the etiopathogenesis and in ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcinogenesis, there is increasing interest in targeting cancer-promoting inflammation as a strategy to treat gastric cancer. Moreover, once cancer develops and anti-cancer immune responses are suppressed, there is evidence of a substantial shift in the microenvironment and new targets for immune therapy emerge. In this chapter, we provide insight into inflammation-related factors, including T lymphocytes, macrophages, pro-inflammatory chemokines and cytokines, which promote H. pylori-associated gastric cancer initiation and growth. While intervening with chronic inflammation is not a new practice in rheumatology or gastroenterology, this approach has not been fully explored for its potential to prevent carcinogenesis or to contribute to the treatment of gastric cancer. This review highlights current and possible strategies for therapeutic intervention including: i) targeting pro-inflammatory mediators, ii) targeting growth factors and pathways involved in angiogenesis in the gastric tumor microenvironment, and iii) enhancing anti-tumor immunity. In addition, we highlight a significant number of clinical trials and discuss the importance of individual tumor characterization towards offering personalized immune-related therapy.

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Section: Anti-cancer Strategies Targeting the Pro-inflammatory Mediatsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 84%

Section: Anti-cancer Strategies Targeting the Pro-inflammatory Mediatmentioning

confidence: 98%

See 1 more Smart Citation

Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy

Piazuelo

Riechelmann

Wilson

et al. 2019

Current Topics in Microbiology and Immunology

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“…Rates of aspirin, metformin, and statins use have increased over the past decades 23 – 25 , but non-adherence to these medications is also common 26 – 28 . To clarify the chemoprotective effect of medication, cumulative medication exposure should be taken into account 29 . Second, another important aspect to be considered is the simultaneous use of medications.…”

Section: Introductionmentioning

confidence: 99%

Population-wide impacts of aspirin, statins, and metformin use on prostate cancer incidence and mortality

Koo

Jeong

Cho

et al. 2021

Sci Rep

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We evaluated the association between aspirin, statins, and metformin use and prostate cancer (PC) incidence and mortality using a large population-based dataset. 388,760 men who participated in national health screening program in Korea during 2002–2003 were observed from 2004 to 2013. Hazard ratios of aspirin, statins, and metformin use for PC incidence and PC mortality were calculated with adjustment for simultaneous drug use. Cumulative use of each drug was inserted as time-dependent variable with 2-year time windows. Aspirin use ≥ 1.5 year (per 2-year) was associated with borderline decrease in PC mortality when compared to non-users (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.50–1.02). Statins use was not associated with either PC incidence or PC mortality. Metformin ever-use was associated with decreased PC incidence compared with non-diabetics (aHR 0.86, 95% CI 0.77–0.96). Diabetics who were not using metformin or using low cumulative doses had higher PC mortality than non-diabetics (aHR 2.01, 95% CI 1.44–2.81, and aHR 1.70, 95% CI 1.07–2.69, respectively). However, subjects with higher cumulative doses of metformin did not show increased PC mortality. In conclusion, metformin use was associated with lower PC incidence. Use of aspirin and that of metformin among diabetic patients were associated with lower PC mortality.

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“…These results have prompted the initiation of randomized clinical trials assessing aspirin as a novel adjuvant treatment to surgery in patients with certain cancer types. Regarding gastric adenocarcinoma specifically, observational studies have indicated that aspirin may reduce its incidence [11][12][13], but there is a paucity of data regarding a potential survival benefit of aspirin as an adjuvant therapy to gastrectomy in patients with this cancer.…”

Section: Introductionmentioning

confidence: 99%

Aspirin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma

et al. 2022

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Background Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. Methods This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75–160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. Results Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85–1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86–1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84–1.15) or 3 years (HR = 0.94, 95% CI 0.79–1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82–1.25). Conclusions Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients.

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Cumulative Dose Threshold for the Chemopreventive Effect of Aspirin Against Gastric Cancer

Abstract: Long-term aspirin use was associated with reduced gastric cancer incidence in the general population of South Korea when the cumulative dose was >3 DDD-years.

Cited by 17 publications

References 34 publications

Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy

Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy

Population-wide impacts of aspirin, statins, and metformin use on prostate cancer incidence and mortality

Aspirin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma

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