Colorectal Cancer Risk 5-times Higher in CF: Population Study
An association was noted between cancer risk, CFTR gene function
The incidence of colorectal cancer (CRC) in people with cystic fibrosis (CF) was five times higher than in those without CF, after adjusting for age, in a large-scale English population study.
CFTR gene mutations, the underlying cause of CF, occurred more frequently than expected, suggesting an association between CFTR function and CRC risk, the researchers noted.
“This increase in predisposition is likely to be multifactorial due to a combination of factors such as CFTR dysfunction, increased local and systemic inflammation, altered gut microbiota [the populations of friendly microbes naturally present in the gut], and the use of high fat and low fibre diets,” the researchers wrote, noting more research is needed to develop effective cancer screening strategies for CF populations.
The study, “The risk of colorectal cancer in individuals with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: An English population-based study,” was published in the Journal of Cystic Fibrosis.
The risk of developing digestive tract cancer, especially CRC, appears to be higher in people with CF compared to the general population. Recent studies investigating F508del, the most common CF-causing genetic defect, reported it elevated in several types of cancer, including CRC.
Because CF is a relatively rare condition with a young age of onset and CRC primarily occurs in older people, there is not enough data on cancer risk in CF patients to inform screening strategies.
Assessing the risk of colorectal cancer with CF
CRC risks in the CF population across England were assessed by researchers in the U.K. Data were collected from three sources: COloRECTal cancer data Repository (CORECT-R), Cystic Fibrosis Trust U.K. CF Registry and Secondary Use Statistics (SUS), and the Genomics England 100,000 Genomes Project.
There was more women in the CF population than in the population without CF (60.7 vs. 44.5%).
CORECT-R data identified 28 people with both CF and CRC. At CRC diagnosis, the median age was significantly lower compared to those without CF diagnosed with CRC (52 vs. 73 years). A quarter of CF patients with CRC were younger than 40, compared to 2.0% in those without CF.
Half (50.0%) of the CF tumors were seen on the right side of the bowel compared to 26.5% in those without CF.
“This is a significant finding as right sided tumours of the colon have been shown to have worse survival and are frequently diagnosed at a later stage, making this group key to any interventional strategies around screening,” the researchers wrote.
With 28 people in the CF/CRC group, compared to a mean CF population of 8,894 people from 2007 to 2017, the crude incidence rate of CRC in CF was 0.29 per 1,000 person-years of follow-up. Comparatively, the CRC incidence rate in those without CF was 0.62 per 1,000 person-years. Person-years is a measurement that accounts for the number of people and the time period investigated.
U.K. CF Registry data also found 28 cases of CRC (2009–2020) in a mean population of 10,242 CF people, representing an incidence rate of 0.23 per 1,000 person-years, “comparable to that which was observed using the CORECT-R data,” the researchers noted.
After adjusting for age, the standardized incidence ratio (SIR), the ratio of observed to expected CRC cases, was five times higher with CF compared to without CF.
CRC incidence rate was higher for people age 50 and older, regardless of CF status. People with CF age 50–69 had 1.65 extra CRC case per 1,000 person-years than those without CF, and one additional case between age 40–49.
The overall rate of CFTR mutations was significantly higher in the CRC population. Among the 2,023 CRC people with genetic information, 141 carried a CFTR mutation.
Overall, 62 (3.1%) had the F508del mutation, which was not different from that seen in other studies, including non-cancer patients (3.15%), according to researchers.
However, the CFTR-R117H mutation, a relatively frequent mutation in CF patients worldwide, was found significantly more often with CRC. Another, called CFTR-G551D, occurred less frequently than in other studies without cancer. F508del and R117H CFTR mutations accounted for more than half seen in this group.
Of the 419 mutations listed in the CFTR2 database as causing CF or of varying clinical consequence, 378 (90·2%) were not identified in the CRC data.
“Individuals with CF and carriers of the CF gene are at increased risk of CRC,” the authors wrote. “A better understanding of the role of CFTR dysfunction in the development and natural history of CRC cancer is needed to inform screening, and [possible] treatment strategies for those with CFTR mutations.”