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Association of Bile Acid Diarrhea With Incidence of Gastrointestinal Cancers
TAKE-HOME MESSAGE
- This Danish registry study involving 5245 individuals with a diagnosis of bile acid diarrhea (BAD; mostly via selenium-homotaurocholic acid testing) found that the cumulative incidence of gastrointestinal cancers over 6 years was 1.6% compared with 1.1% over the same time frame for matched controls without BAD (P = .01). The gastrointestinal cancer–related mortality was higher among those with BAD than among controls (0.9% vs 0.5%).
- There is a need for increased awareness about preventive measures and early gastrointestinal cancer detection among patients with BAD. Further studies are needed to explore any possible carcinogenic risk of BAD.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
Bile acid diarrhea (BAD) is an underrecognized and socially debilitating disease caused by high concentrations of bile acids in the colon. Bile acids directly and indirectly promote carcinogenesis. Here, we investigated if individuals with BAD have an increased risk of gastrointestinal (GI) cancers.
DESIGN
By using the Danish health registries, adult individuals with BAD were identified by international classification of disease 10th revision (ICD10) code K90.8 or referral to the diagnostic ⁷⁵selenium-homotaurocholic acid test followed by prescription of a bile acid sequestrant within 365 days (n=5,245). Age and sex-matched individuals without BAD were included for comparison (n=52,450). We analyzed the cumulative incidence of GI cancers after BAD diagnosis and the odds ratios (ORs) of GI cancer eight and 15 years before BAD diagnosis/matching.
RESULTS
Cumulative incidence of GI cancer six years after BAD diagnosis/matching was 1.6% in the BAD group and 1.1% in controls (p=0.01). The ORs of total GI cancer eight and 15 years before BAD diagnosis were 6.16 (5.08-7.48) and 5.19 (4.28-6.29), respectively. Furthermore, 47 individuals with BAD (0.9%) and 250 (0.5%) controls died of GI cancer.
CONCLUSION
This nationwide cohort study indicates an association between BAD and GI cancers. We found both a higher incidence of GI cancer after BAD diagnosis compared with controls and increased OR of GI cancer before BAD diagnosis. Bearing in mind the underdiagnosis of BAD, the delay of BAD diagnosis, and the carcinogenic effect of bile acids, these findings warrant further investigations of the risk of GI cancer in individuals with BAD.
Additional Info
Disclosure statements are available on the authors' profiles:
Bile Acid Diarrhea is Associated with an Increased Incidence of Gastrointestinal Cancers
Am. J. Gastroenterol 2024 May 08;[EPub Ahead of Print], AM Ellegaard, ML Kårhus, M Winther-Jensen, FK Knop, LL KårhusFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Ellegard et al present data based on the Danish health registries showing that the cumulative incidence of gastrointestinal (GI) cancer was higher among 5245 individuals with bile acid (BA) diarrhea (BAD) than among 52,450 matched controls from the general population. Increased GI cancer risks were observed 8 and 15 years prior to BAD diagnosis and were confirmed when excluding individuals with prior GI surgery.
The association between colonic BA and risk of colon cancer has been documented in preclinical models, prospective studies of fecal BA and colorectal cancer, systematic reviews of observational studies, and mechanistic studies documenting the effects of di-α hydroxy BAs (eg, deoxycholic acid) on colonic mucosal proliferation and inhibition of genobiotic-metabolizing enzymes potentially playing a role in carcinogenesis. It is important to appreciate that approximately 1% of the general population has BAD.
The counter argument to the potential BA carcinogenesis was the observation that even a duration of 25 years after partial ileal bypass for control of hyperlipidemia was not associated with increased incidence of colon cancers.
Overall, the results indicate an association of BAD with GI cancer. The observation that the risk of GI cancers was observed even 15 years prior to the diagnosis of BAD leads to important conclusions: first, the need for early GI cancer detection among individuals suffering from BAD; and, second, the importance of positively diagnosing BAD using gold-standard tests now available (eg, 75selenium-homotaurocholic acid retention, 48-h fecal bile acids, and a combination of serum 7αC4 levels and percent primary bile acids in a single stool sample). Finally, more research is needed on causal links between BAD and GI cancers.