Abstract
Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers.
Highlights
Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, 20141 Milan, Italy; Department of Neuroscience, Imaging and Clinical Sciences, and CAST, “G. d’Annunzio” University, Division of Gastroenterology and Digestive Endoscopy, IRCCS, Regina Elena National Cancer Institute, Center for Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, Hospital Pharmacy Unit, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Ambulatorio Familiarita’ Neoplastica UOC Oncologia Medica ULSS5 Polesana, 45100 Rovigo, Italy; Proposal Paper from A.I.F.E.G. (Associazione Italiana per lo Studio della Familiarità ed Ereditarietà dei Tumori Gastrointestinali)
Reduced risk of colorectal cancer (CRC) was detected in the long-term observational follow-up of the Women’s Health Study where aspirin was administered in alternate-day 100-mg aspirin versus placebo [34]. These findings suggest that the chemopreventive effect of aspirin recapitulates its antiplatelet effect, i.e., a long-lasting duration [29] and, most importantly, its saturability at low doses [35]
Is controversial since in the CAPP2 study higher BMI was associated with an increased aspirin benefit [60], whereas other data suggest that aspirin efficacy could be reduced by high BMI [61]; excess body fat is a modifiable cancer risk factor [62], and platelet activation is associated with obesity [63]; aspirin might be beneficial to cancer patients with obesity; it was reported that obesity affects aspirin metabolism in several ways that reduce its inhibitory effect on platelet function [64]; clinical studies are ongoing by Patrignani’s group to verify whether aspirin antiplatelet effects could be improved by increasing the aspirin dose or shortening its dosing interval in CRC patients with obesity
Summary
Cancer prevention for the general population is commonly associated with screening programs with early detection to lower cancer mortality as the primary endpoint. In parallel to this approach, preventive interventions strategies have been investigated to reduce cancer incidence. Helsingen’s proposal avoids CRC screening for very low-risk populations; we should consider more accurate screening tests for high-risk individuals to improve effectiveness even if this is more invasive This strategy requires an active interaction between healthcare providers and the population to identify individual risk and to reach a proper balance between health assistance and personal preferences, the potential benefits and disadvantages of the test/program offered, and to obtain a real shared and informed decision.
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