Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement

Cuzick, Jack; Otto, Florian; Baron, John A.; Brown, Powel H.; Burn, John; Greenwald, Peter; Jankowski, Janusz; Vecchia, Carlo La; Meyskens, Frank L.; Senn, Hans; Thun, Michael J.

doi:10.1016/s1470-2045(09)70035-x

Cited by 650 publications

(514 citation statements)

References 57 publications

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“…Celecoxib (2 Â 400 mg/day) was shown to significantly reduce the number of colorectal and duodenal polyps in familial adenomatous polyposis patients (Steinbach et al, 2000), and is now approved as adjunctive therapy to decrease the risk of CRC development in familial adenomatous polyposis patients (Bertagnolli et al, 2009). Long-term use of high doses of COXIBs as chemopreventive strategy in sporadic CRC, however, is not recommended because of the elevated risk of potentially severe cardiovascular complications (Cuzick et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

et al. 2011

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Cyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and progression, in particular of the colon. The COXIB celecoxib is approved for adjunct therapy in patients with Familial adenomatous polyposis at high risk for colorectal cancer (CRC) formation. Long-term use of COXIBs, however, is associated with potentially severe cardiovascular complications, which hampers their broader use as preventive anticancer agents. In an effort to better understand the tumor-suppressive mechanisms of COXIBs, we identified MAGUK with Inverted domain structure-1 (MAGI1), a scaffolding protein implicated in the stabilization of adherens junctions, as a gene upregulated by COXIB in CRC cells and acting as tumor suppressor. Overexpression of MAGI1 in CRC cell lines SW480 and HCT116 induced an epitheliallike morphology; stabilized E-cadherin and b-catenin localization at cell-cell junctions; enhanced actin stress fiber and focal adhesion formation; increased cell adhesion to matrix proteins and suppressed Wnt signaling, anchorage-independent growth, migration and invasion in vitro. Conversely, MAGI1 silencing decreased Ecadherin and b-catenin localization at cell-cell junctions; disrupted actin stress fiber and focal adhesion formation; and enhanced Wnt signaling, anchorage-independent growth, migration and invasion in vitro. MAGI1 overexpression suppressed SW480 and HCT116 subcutaneous primary tumor growth, attenuated primary tumor growth and spontaneous lung metastasis in an orthotopic model of CRC, and decreased the number and size of metastatic nodules in an experimental model of lung metastasis. Collectively, these results identify MAG1 as a COXIBinduced inhibitor of the Wnt/b-catenin signaling pathway, with tumor-suppressive and anti-metastatic activity in experimental colon cancer.

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Section: Introductionmentioning

confidence: 99%

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

et al. 2011

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“…C/C (4) C/T (40) T/T An association between rs5275 and familial cancer J Ross et al genotype carriers. Little can be stated regarding male CC carriers as there were only four observations.…”

Section: Variant Screeningmentioning

confidence: 99%

“…3 Aspirin and other nonsteroidal antiinflammatory inhibitors of COX-2 are known to act as CRC chemopreventatives. 4 COX-2 is known to be overexpressed in B85% of human colorectal carcinomas, 50% of colorectal adenomas, 5 as well as other epithelial and nonepithelial tumours (reviewed in Koki and Masferrer 6 ). There is evidence that COX-2 overexpression is also involved in the aetiology of familial adenomatous polyposis (FAP), a CRC predisposition syndrome caused by an inherited mutation of the Adenomatous polyposis coli (APC) gene.…”

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confidence: 99%

An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk in families with inherited non-syndromic predisposition

et al. 2013

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Recently our group completed a genome-wide linkage study investigating Australian and Spanish families with inherited risk of colorectal cancer (CRC). A minor linkage peak from that study located on chromosome 1 correlates with the location of a known CRC risk-modifying gene, prostaglandin synthase (PTGS2). PTGS2 encodes the inducible prostaglandin synthase enzyme cyclooxygenase-2 (COX-2). Prostaglandins are implicated in the initiation of carcinogenesis and progression of tumours. Sequencing of PTGS2 in a small subset of affected individuals identified a high frequency of the minor C allele of single nucleotide polymorphism rs5275. We then genotyped the rs5275 polymorphism in 183 affected and 223 unaffected individuals from our CRC predisposed families. Tests for association in the presence of linkage were made using family-based association tests. The C allele was found to be significantly associated (Po0.01) with diagnosis of hereditary non-syndromic CRC (P ¼ 0.0094, dominant model) and an earlier age of diagnosis (P ¼ 0.0089, heterozygous-advantage model). Interestingly, by stratifying the age of diagnosis data, we observed a speculative gender-discordant effect. Relative to other groups, female CC carriers were diagnosed less when young, but by 60 years of age were the most at risk group. Conversely, CT carriers of both genders showed a consistently earlier diagnosis relative to TT carriers. Our results suggest potential differential age-and genderdependent efficacies of chemopreventative COX-2 inhibitors in the context of non-syndromic colorectal cancer.

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“…6 Aspirin, 7 nonsteroidal anti-inflammatory medications 8 , and statins 9 have been hypothesized to reduce the incidence of prostate cancer. However, although there are several preclinical and epidemiologic studies supporting a protective effective of anti-inflammatory therapies for prostate cancer, as yet there have been no clinical trials.…”

Section: General Principles Of Disease Preventionmentioning

confidence: 99%

Prostate cancer prevention: concepts and clinical recommendations

Silberstein

Parsons

2010

Prostate Cancer Prostatic Dis

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Prevention is an important strategy for limiting prostate cancer morbidity and mortality. Two major types of prevention are primary (reduction of incident cases) and tertiary (inhibition of disease progression and recurrence). Pharmacological and dietary interventions have potential functions in both the primary and tertiary prevention of prostate cancer. Five-a reductase inhibitors (5-ARIs) reduce the incidence of prostate cancer in both general and higher-risk populations and are currently under study for tertiary prevention in active surveillance and biochemical recurrence patients. Selenium, vitamin E, and vitamin C do not prevent incident prostate cancer in the general population; however, other promising diet-based interventions are currently under study for tertiary prevention. We recommend consideration of 5-ARIs for prostate cancer prevention in (1) asymptomatic men with a PSA p3.0 ng ml -1 who are undergoing or anticipate undergoing PSA screening for early detection of prostate cancer and (2) asymptomatic men with PSA X2.5 and p10 ng ml -1 and an earlier prostate biopsy negative for cancer. Men should be informed of the potential risks of 5-ARI therapy. Currently, there is neither clinical evidence to support the use of 5-ARIs for tertiary prevention in active surveillance or biochemical recurrence populations, nor micronutrients for prostate cancer prevention of any type.

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Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement

Cited by 650 publications

References 57 publications

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk in families with inherited non-syndromic predisposition

Prostate cancer prevention: concepts and clinical recommendations

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