Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer

Ye, Shinheeye; Lee, Myeongjee; Lee, Dong Hoon; Ha, Eun–Hee; Chun, Eun Mi

doi:10.1001/jamanetworkopen.2019.0185

Cited by 36 publications

(33 citation statements)

References 42 publications

(45 reference statements)

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“…The selection of LD ASA, the dosing schedules and duration of intervention may have led to the minimal effects on the pre-selected gene-expression signatures. Although a body of data supports the development of LD ASA in lung cancer chemoprevention (32,33), it is possible that regular-strength ASA might have yielded more robust modulation of the gene signatures in the anti-carcinogenic direction. An additional arm of regular-strength ASA would have strengthened the study by addressing doseresponse in modulating risk of tobacco exposure and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial

Garland

Guillen-Rodriguez

Hsu

et al. 2019

Cancer Prevention Research

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A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, doubleblinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Lowdose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of À4.55 AE 11.52 from baseline 15.44 AE 13.79 ng/mg creatinine for arms combined, P ¼ 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature (P < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.

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Section: Discussionmentioning

confidence: 99%

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial

Garland

Guillen-Rodriguez

Hsu

et al. 2019

Cancer Prevention Research

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“… 49 These results are consistent with those observed from a study on about 10 000 cancer samples across 21 cancer types in The Cancer Genome Atlas. 50 Both studies are based on 15 Buffa signatures instead of low-oxygen level as a direct indicator because it is not contained in the databases. Moreover, higher hypoxic signaling and hypoxia-associated genes tend to occur in tumors with higher diversity and are correlated with a poorer overall survival (OS) and progression-free survival (PFS).…”

Section: Hallmarks Of Tmementioning

confidence: 99%

“…In a study on the role of aspirin in reducing cancer risk, various doses, frequencies, and duration have been selected, such as the following: ≥975 mg/w for more than 5 years, 177 ≥150 mg/d for more than 1 year, 178 ≥325 mg/d for more than 5 years, 179 600 mg/d for a mean of 25 months, 180 100 mg/d for at least 104 d/y. 50 Similarly, when assessing aspirin’s role in combination with other treatment modalities, these indices should also be carefully selected. Gastrointestinal bleeding is always a concern when using aspirin.…”

Section: Conventional Drugs With New Use: Candidate For Tme-targetingmentioning

confidence: 99%

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

717

483

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Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

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“…65 A large retrospective study including more than 10 million people in South Korea confirmed that long-term use of low-dose aspirin was associated with a decreased risk of lung cancer. 66 Recognition of the tumorpromoting effects of platelets emphasizes the role of antiplatelet therapy in the prevention and treatment of cancer. Nevertheless, identifying cancer patients who will benefit from antiplatelet therapy is still an important issue.…”

Section: Discussionmentioning

confidence: 99%

<p>Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma</p>

Qu¹,

Li²,

Tang³

et al. 2020

CMAR

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Purpose: Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. Patients and Methods: The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. Results: We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count <300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001). Conclusion: Elevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.

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Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer

Cited by 36 publications

References 42 publications

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial

Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial

The updated landscape of tumor microenvironment and drug repurposing

<p>Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma</p>

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