Increased gastrointestinal cancer risk in cystic fibrosis: Screening, prevention, and future directions

The marked improvement in life expectancy from advances in treatment for cystic fibrosis has focused attention on diseases of aging. Cystic fibrosis (CF) is associated with increased risk for digestive system malignancies, including colorectal cancer and pancreaticobiliary cancers. Although risk factors for gastrointestinal malignancy include solid organ transplant and older age, people with CF may present with cancer at a younger age than the general population. Potential mechanisms for increased digestive cancer susceptibility include the underlying genetic defect, dietary patterns, or alterations in the gut microbiome. The impact of cystic fibrosis transmembrane regulator modulator therapies on gastrointestinal cancer risk remains unclear. Our review summarizes the previously published consensus screening recommendations for colorectal cancer, which endorsed starting colonoscopy at age 30 in patients with history of transplant and at age 40 in patients without a transplant. Recent work evaluating the use of non invasive testing for colorectal cancer is reviewed. We propose screening practices for non-colorectal cancers based on the limited evidence to date. We discuss potential preventative approaches and conclude with future directions to improve our ability to address this growing problem. Future work should focus on a greater understanding of the underlying mechanisms of pathogenesis at a molecular level, clinical risk factors for gastrointestinal malignancies at a population level, and preventative strategies.