Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

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.

Determinants of adherence to recommendations on physical activity, red and processed meat intake, and body weight among lynch syndrome patients

“…Health care providers involved in (follow-up) care for LS patients (such as genetic counsellors, clinical geneticists, gastro-enterologists, gynaecologists) could easily incorporate providing WCRF-NL health promotion materials during counselling or surveillance visits with LS patients. Informing LS patients about lifestyle-related factors (including the preventive use of aspirin [45]) and cancer risk is in line with current guidelines for LS patients [16]. Increasing knowledge, by providing health promotion materials or referring to online health education material (e.g., via the international and national websites of the WCRF such as www.wcrf.org), is an important first step to achieve adherence.…”

“…First, univariable logistic regression analyses were conducted with adherence to one of the WCRF recommendations on body weight, physical activity, or red and processed meat intake as dependent dichotomous variable, and a single potential determinant as independent variable. The following potential demographic determinants were included as independent variables: gender (male, female); age (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), and 55-73 years), education level (low, medium, high), and marital status (partner, no partner). The following potential health-related determinants were included: years since LS diagnosis (0-2 years, 2-4 years, and 4-20 years), colon surgery (yes, no), personal cancer history (yes, no), and smoking status (current, ex-, never smoker).…”

Lynch Syndrome: From Carcinogenesis to Prevention Interventions

“…In a dedicated review, Patrignani and Patrono provided an interesting framework, based on the phenotype switching of colonic cells toward cancer cells, a process induced by the platelets activated via the COX pathway [ 101 ]. Moreover, in a more recent paper, Serrano et al [ 102 ] presented revised data and recommendations about aspirin and cancer chemoprevention in LS. At the moment, only one chemoprevention clinical trial in LS patients has been completed, the CAPP-2 (Cancer Prevention Program 2), and its results have been published.…”

Risk factors of malignancy

“…Аспирин и другие нестероидные противовоспалительные препараты В исследованиях показано, что регулярное применение аспирина и других нестероидных противовоспалительных препаратов (НПВП) снижает риск аденоматозных полипов и колоректального рака на 20-40% [165][166][167][168]. Рандомизированное контролируемое исследование показало, что у пациентов с высоким риском синдрома Линча прием 600 мг аспирина в день снижает риск колоректального рака на 60 процентов [169].…”

“…При подборе рекомендаций и анализе получаемых пациентом препаратов необходимо сопоставлять потенциальные преимущества долгосрочной терапии с потенциальными побочными эффектами (гастродуоденальная токсичность и повышенный сердечно-сосудистый риск при использовании неаспириновых НПВП), учитывая наличие скрининга колоректального рака [165][166][167][168][169][170][171].…”