Aspirin and cancer risk: a quantitative review to 2011

Bosetti, Cristina; Rosato, Valentina; Gallus, Silvano; Cuzick, Jack; Vecchia, Carlo La

doi:10.1093/annonc/mds113

Cited by 272 publications

(258 citation statements)

References 101 publications

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“…Our findings of the EP2 expression in TAFs in the mesenchyme are consistent with our previous finding that EP2 was expressed in stromal region in Apc D716 mice and Ptger2 deficiency suppressed intestinal polyp formation (43). Furthermore, several studies reported expression of EP2 in various types of cancers (44)(45)(46) and aspirin lowers the risk of solid tumors other than colorectal cancer (4,5). It is interesting to test how widely the EP2 actions we found here operate in microenvironment of cancers other than colorectal cancer.…”

Section: Ly-6gsupporting

confidence: 91%

“…One major risk factor of colorectal cancer is inflammatory bowel diseases such as ulcerative colitis (2), indicating that the pathogenesis of colorectal cancer is closely associated with inflammatory responses in the colon, and that manipulation of inflammation might prevent colorectal cancer development. In fact, it is well known that the use of aspirin or other NSAIDs is associated with reduction of risk of colorectal cancer (3)(4)(5). NSAIDs, including aspirin, exert their effects by inhibiting COX, an enzyme initiating prostaglandin (PG) biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

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Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

et al. 2015

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Inflammation in the colon contributes significantly to colorectal cancer development. While aspirin reduces the colorectal cancer risk, its action mechanism, especially in inflammation in tumor microenvironment, still remains obscure. Here, we examined this issue by subjecting mice deficient in each prostaglandin (PG) receptor to colitis-associated cancer model. Deficiency of PGE receptor subtype EP2 selectively reduced, and deficiency of EP1 and EP3 enhanced, the tumor formation. EP2 is expressed in infiltrating neutrophils and tumor-associated fibroblasts in stroma, where it regulates expression of inflammation-and growth-related genes in a self-amplification manner. Notably, expression of cytokines such as TNFa and IL6, a chemokine, CXCL1, a PG-producing enzyme, COX-2, and Wnt5A was significantly elevated in tumor lesions of wild-type mice but this elevation was significantly suppressed in EP2-deficient mice. Intriguingly, EP2 stimulation in cultured neutrophils amplified expression of TNFa, IL6, CXCL1, COX-2, and other proinflammatory genes synergistically with TNFa, and EP2 stimulation in cultured fibroblasts induced expression of EP2 itself, COX-2, IL6, and Wnt genes. EP2 expression in infiltrating neutrophils and tumor-associated fibroblasts was also found in clinical specimen of ulcerative colitis-associated colorectal cancer. Bone marrow transfer experiments suggest that EP2 in both cell populations is critical for tumorigenesis. Finally, administration of a selective EP2 antagonist potently suppressed tumorigenesis in this model. Our study has thus revealed that EP2 in neutrophils and tumor-associated fibroblasts promotes colon tumorigenesis by amplifying inflammation and shaping tumor microenvironment, and suggests that EP2 antagonists are promising candidates of aspirin-alternative for chemoprevention of colorectal cancer.

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Section: Ly-6gsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

et al. 2015

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“…Aspirin has been reported to prevent carcinogenesis of colorectal cancer in Apc Min/þ mice and prevent 44% tumor formation at a dosage of 200 mg/kg through attenuating inflammation (31,32). However, its clinical use for chemoprevention is prohibited due to a significant incidence of gastrointestinal upset and bleeding.…”

Section: Clin Cancer Res; 22(16) August 15 2016mentioning

confidence: 99%

Prevention of Colitis and Colitis-Associated Colorectal Cancer by a Novel Polypharmacological Histone Deacetylase Inhibitor

Wei

Lin

Tseng

et al. 2016

Clinical Cancer Research

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Purpose: Colorectal cancer is a worldwide cancer with rising annual incidence. Inflammation is a well-known cause of colorectal cancer carcinogenesis. Metabolic inflammation (metaflammation) and altered gut microbiota (dysbiosis) have contributed to colorectal cancer. Chemoprevention is an important strategy to reduce cancer-related mortality. Recently, various polypharmacologic molecules that dually inhibit histone deacetylases (HDAC) and other therapeutic targets have been developed.Experimental Design: Prevention for colitis was examined by dextran sodium sulfate (DSS) mouse models. Prevention for colorectal cancer was examined by azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models. Immunohistochemical staining was utilized to analyze the infiltration of macrophages and neutrophils and COX-II expression in mouse tissue specimens. The endotoxin activity was evaluated by Endotoxin Activity Assay Kit.Results: We synthesized a statin hydroxamate that simultaneously inhibited HDAC and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Its preventive effect on colitis and colitis-associated colorectal cancer in mouse models was examined. Oral administration of this statin hydroxamate could prevent acute inflammation in the DSS-induced colitis and AOM/ DSS-induced colorectal cancer with superior activity than the combination of lovastatin and SAHA. It also reduced proinflammatory cytokines, chemokines, expression of COX-II, and cyclin D1 in inflammation and tumor tissues, as well as decreasing the infiltration of macrophages and neutrophils in tumor-surrounding regions. Stemness of colorectal cancer and the release of endotoxin in AOM/DSS mouse models were also attenuated by this small molecule.Conclusions: This study demonstrates that the polypharmacological HDAC inhibitor has promising effect on the chemoprevention of colorectal cancer, and serum endotoxin level might serve as a potential biomarker for its chemoprevention. Clin Cancer Res; 22(16); 4158-69. Ó2016 AACR.

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“…On the basis of well-established associations with colorectal cancer risk (8)(9)(10)25), the following predictors were selected: age, BMI, sex, prevalent diabetes, previous colorectal cancer screening, first-degree relative with colorectal cancer, aspirin use, smoking status (never, former, and current), alcohol intake, cereal consumption and wholegrain bread as markers of dietary fiber intake, intake of vegetables, fruits, red meat and processed meat, and vigorous physical activity.…”

Section: Model Developmentmentioning

confidence: 99%

Development and Validation of a Risk Score Predicting Risk of Colorectal Cancer

Steffen

MacInnis

Joshy

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Quantifying the risk of colorectal cancer for individuals is likely to be useful for health service provision. Our aim was to develop and externally validate a prediction model to predict 5-year colorectal cancer risk.Methods: We used proportional hazards regression to develop the model based on established personal and lifestyle colorectal cancer risk factors using data from 197,874 individuals from the 45 and Up Study, Australia. We subsequently validated the model using 24,233 participants from the Melbourne Collaborative Cohort Study (MCCS).Results: A total of 1,103 and 224 cases of colorectal cancer were diagnosed in the development and validation sample, respectively. Our model, which includes age, sex, BMI, prevalent diabetes, ever having undergone colorectal cancer screening, smoking, and alcohol intake, exhibited a discriminatory accuracy of 0.73 [95% confidence interval (CI), 0.72-0.75] and 0.70 (95% CI, 0.66-0.73) using the development and validation sample, respectively. Calibration was good for both study samples. Stratified models according to colorectal cancer screening history, that additionally included family history, showed discriminatory accuracies of 0.75 (0.73-0.76) and 0.70 (0.67-0.72) for unscreened and screened individuals of the development sample, respectively. In the validation sample, discrimination was 0.68 (0.64-0.73) and 0.72 (0.67-0.76), respectively. Conclusion: Our model exhibited adequate predictive performance that was maintained in the external population.Impact: The model may be useful to design more powerful cancer prevention trials. In the group of unscreened individuals, the model may be useful as a preselection tool for population-based screening programs. Cancer Epidemiol Biomarkers Prev; 23(11); 2543-52. Ó2014 AACR.

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Aspirin and cancer risk: a quantitative review to 2011

Cited by 272 publications

References 101 publications

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth

Prevention of Colitis and Colitis-Associated Colorectal Cancer by a Novel Polypharmacological Histone Deacetylase Inhibitor

Development and Validation of a Risk Score Predicting Risk of Colorectal Cancer

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