Shiab Mussad, MD1, Gavisha Waidyaratne, MD2, Joanna Jiang, MD3, Maegan E. Roberts, MS4, Yevgeniya Gokun, MS2, Spencer Harris, MS4, Peter P. Stanich, MD1, Phil Hart, MD5, Luis Lara, MD2, Somashekar Krishna, MD1, Peter Lee, MD1, Samuel Han, MD2, Georgios I. Papachristou, MD, PhD1, Mitchell Ramsey, MD1 1The Ohio State Wexner Medical Center, Columbus, OH; 2The Ohio State University Wexner Medical Center, Columbus, OH; 3The Ohio State University Medical Center, Columbus, OH; 4Ohio State University, Columbus, OH; 5The Ohio State University, Columbus, OH
Introduction: Pathogenic variants (PVs) in CFTR are risk factors for pancreatitis and may increase the risk of gastrointestinal malignancies, including pancreatic cancer (PC). The aim of this study was to describe the CFTR PVs among subjects with PC, including subjects with and without cystic fibrosis (CF).
Methods: A systematic search was performed on 5/16/2023 in PubMed and Embase, using synonyms for CFTR and pancreatic cancer. We included all manuscripts and abstracts published in English that reported the prevalence of CFTR PVs in human subjects with PC or that reported the prevalence of PC among subjects with CF. A chi square test with Yates correction was used to determine differences between subgroups.
Results: The search strategy produced 1333 studies published between 1963 and 2023. After excluding studies that did not meet inclusion criteria, 9 CF and 14 non-CF studies were included. Among PC subjects without CF, 222/3969 (5.59%) were found to have at least one CFTR PV. Twenty-eight unique CFTR PVs were reported, with the most commonly observed being F508del (n=107), W1282X (n=6), R117H (n=6), N1303K (n=4), G970D (n=3), G551D (n=2), Y1014C (n=2), and R74W (n=2). Among PC subjects with CF, 6 studies reported incidence and total person-years of follow up (Table 1). PC was identified in 5 cases; the overall incidence of PC in CF is 1.30 per 100,000 person-years. Subgroup analyses identified a higher incidence among subjects with prior lung transplant compared to those without a history of lung transplant (24.3 vs. 0.797 cases per 100,000 person-years, p=0.003). The CFTR PVs were available for 3 cases of PC in CF (2 cases of pancreatic ductal adenocarcinoma diagnosed at age 36 and 39, 1 case of mucinous cystadenocarcinoma diagnosed at age 19) and all cases were homozygous for F508del. No other germline variants were assessed or reported for these 3 subjects.
Discussion: In patients without CF, specific CFTR PVs (such as F508del or N1303K) may confer higher risk for PC than other PVs, which will require additional investigation. There is insufficient information on the genetics of PDAC in CF to identify a high-risk genotype. The relationship between CFTR PVs and PC needs to be studied further to determine whether PC screening may be warranted among patients with CF or CFTR carriers.
Figure: Table 1. All studies reporting the incidence of pancreatic cancer among subjects with cystic fibrosis (CF).
Disclosures:
Shiab Mussad indicated no relevant financial relationships.
Gavisha Waidyaratne indicated no relevant financial relationships.
Joanna Jiang indicated no relevant financial relationships.
Mitchell Ramsey indicated no relevant financial relationships.
Shiab Mussad, MD1, Gavisha Waidyaratne, MD2, Joanna Jiang, MD3, Maegan E. Roberts, MS4, Yevgeniya Gokun, MS2, Spencer Harris, MS4, Peter P. Stanich, MD1, Phil Hart, MD5, Luis Lara, MD2, Somashekar Krishna, MD1, Peter Lee, MD1, Samuel Han, MD2, Georgios I. Papachristou, MD, PhD1, Mitchell Ramsey, MD1. P2864 - The Cystic Fibrosis Transmembrane Conductance Regulator Gene and the Risk of Pancreatic Cancer: A Systematic Review, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
