Effect of Aspirin or Resistant Starch on Colorectal Neoplasia in the Lynch Syndrome

Burn, John; Bishop, D. Timothy; Mecklin∥, Jukka–Pekka; Macrae, Finlay; Möslein, Gabriela; Olschwang, Sylviane; Bisgaard, Marie Luise; Ramesar, Raj; Eccles, Diana; Maher, Eamonn R.; Bertario, Lucio; Järvinen, Heikki; Lindblom, Annika; Evans, D. Gareth; Lubiński, Jan; Morrison, Patrick J.; Ho, Judy W. C.; Vasen, Hans F. A.; Side, Lucy; Thomas, Huw; Scott, Rodney J.; Dunlop, Malcolm G.; Barker, Geoffrey; Elliott, Faye; Jass, Jeremy R.; Fodde, Riccardo; Lynch, Henry T.; Mathers, John C.

doi:10.1056/nejmoa0801297

Cited by 266 publications

(187 citation statements)

References 21 publications

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“…There is good evidence (level 1b) that medical therapy with aspirin reduces CRC risk in patients with Lynch syndrome. A recent randomized clinical trial (RCT) showed a significant reduction in CRC and other cancers among Lynch syndrome patients who received aspirin 600 mg (Burn et al, 2008;Burn et al, 2011;Chan et al, 2012). A subsequent meta-analysis examining daily aspirin use and its effect on cancer revealed a reduced risk of CRC mortality among aspirin-treated patients, although no greater benefit was achieved with an aspirin dosage above 75 mg daily .…”

Section: Rev Ised Bethesda Guidelinesmentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

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Section: Rev Ised Bethesda Guidelinesmentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

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“…To date, there are two controlled randomized trials that primarily evaluated the efficacy of aspirin in high-risk CRC patients: the Colorectal Adenoma/Carcinoma Programme (CAPP)1 [22] , which included 206 young individuals with a diagnosis of familial adenomatous polyposis (FAP), and CAPP2 [23] , which studied 1009 patients with Lynch syndrome. Both studies compared aspirin (600 mg/d), with or without resistant starch or resistant starch placebo.…”

Section: Clinical Effects Of Aspirin In High-risk Populations: Familimentioning

confidence: 99%

Aspirin, cyclooxygenase inhibition and colorectal cancer

Sostres

Gargallo

Lanas

2014

WJGPT

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Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resourcepoor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Aspirin; Colorectal cancer; Cyclooxygenase inhibition; Mechanisms; Risk; Benefits Core tip: Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Currently, CRC screening programs are not widely available and need to be improved. New prevention strategies are therefore necessary. Daily low-dose aspirin, as given for the prevention of cardiovascular disease events, has demonstrated benefits in clinical and basic studies in terms of preventing adenoma recurrence and decreasing the incidence of CRC and attributable mortality. These findings indicate that the antiplatelet action of aspirin plays a central role in its antitumor effect. Cyclooxygenasedependent and independent mechanisms have been suggested to explain this effect. Extensive translational medical research is mandatory for future progress in CRC prevention.Sostres C, Gargallo CJ, Lanas A. Aspirin, cyclooxygenase inhibition and colorectal cancer.

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“…Several compounds have been suggested including anti-inflammatory agents such as aspirin, which has been shown to reduce the risk of cancer in LS (30). Tumor-maturing agents such as retinoids and, more recently, checkpoint inhibitors can be considered as "tumor preventive tools."…”

Section: Therapeutic Considerationsmentioning

confidence: 99%

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

Tabori

Hansford

Achatz

et al. 2017

Clinical Cancer Research

185

202

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Replication proofreading is crucial to avoid mutation accumulation in dividing cells. In humans, proofreading and replication repair is maintained by the exonuclease domains of DNA polymerases and the mismatch repair system. Individuals harboring germline mutations in genes involved in this process are at increased risk of early cancers from multiple organs. Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1, and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency or constitutional mismatch repair deficiency syndrome (CMMRD). Data gathered in the last decade allow us to better define the clinical manifestations, tumor spectrum, and diagnostic algorithms for CMMRD. In this article, we summarize this information and present a comprehensive consensus surveillance protocol for these individuals. Ongoing research will allow for further definition of replication repairdeficient cancer syndromes, assessing the cost-effectiveness of such surveillance protocols and potential therapeutic interventions for these children and families. Clin Cancer Res; 23(11); e32-e37. Ó2017 AACR.See all articles in the online-only CCR Pediatric Oncology Series.

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Effect of Aspirin or Resistant Starch on Colorectal Neoplasia in the Lynch Syndrome

Abstract: T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 359;24 www.nejm

Cited by 266 publications

References 21 publications

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Aspirin, cyclooxygenase inhibition and colorectal cancer

Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

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