Aspirin May Lower Risk for Bile Duct Cancer

Pam Harrison

April 22, 2016

People who take low-dose aspirin have a significantly lower risk of developing bile duct cancer than nonusers, new research shows.

The findings add to the already substantial evidence that aspirin has chemoprotective properties, especially against gastrointestinal cancers.

"Our study found that individuals who took aspirin had more than a two-and-a-half- to three-and-a-half-fold lesser chance of developing bile duct cancer compared to individuals who did not take aspirin," senior author Lewis Roberts, MB, ChB, PhD, Mayo Clinic, Rochester, Minneapolis, said in a statement.

The study was published online April 19 in Hepatology.

All patients with cholangiocarcinoma (CCA) seen at the Mayo Clinic in Rochester from January 2000 through December 2014 were included in the analysis. The final cohort included 2395 patients with CCA. Patients were classified into three groups, depending on the subtype of CCA they had: intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA).

As investigators explain, these three subtypes are thought to be separate diseases because of differences in the way they present, their treatment course, and patients' prognoses.

A total of 4769 control personss were selected from the Mayo Clinic Biobank dataset.

Participants were designated as current aspirin users if they were taking aspirin at least once a week. Aspirin doses were classified as being either low-dose (81 to 162 mg/day) or high-dose (≥325 mg/day).

Overall, 591 (24.7%) patients with CCA and 2129 (44.6%) control participants took aspirin.

Patients who developed one of the three subtypes of CCA were 59% less likely to be taking aspirin than control persons (P < .001), reports lead author Jonggi Choi, MD, formerly with the Mayo Clinic College of Medicine, in Rochester, where the research was done.

The adjusted odds ratios (AORs) in favor of aspirin users being protected against bile duct cancer were also relatively consistent across the three CCA subtypes, he adds.

Compared with nonusers, current aspirin users had a 65% lower risk of developing iCCA, at an AOR of 0.35; a 66% lower risk of developing pCCA, at an AOR of 0.34; and a 71% lower risk of developing dCCA, at an AOR of 0.29 (P < .001 for all three comparisons).

The protective effect of aspirin was variable among users who had been taking aspirin for more than 3 years relative to those who had been taking aspirin for 3 years or less, as well as between high-dose and low-dose aspirin users, but it was not different between those who took aspirin on a daily vs nondaily basis.

Table. Association Between Duration, Dosage, and Frequency of Aspirin Use and CCA Risk

Variable Case Patients (%) Control Patients (%) AOR P Value
Duration of use        
≤3 years 4.3 9.1 0.30 <.001
>3 years 6.7 33.1 0.12 <.001
Low 16.0 35.6 0.29 <.001
High 5.9 9.0 0.39 <.001
Nondaily 1.3 2.5 0.35 <.001
Daily 23.4 42.1 0.34 <.001


Continuous, Unremitting Inflammation

"We know that continuous, unremitting inflammation is one of the main factors that promotes cancer of the bile ducts," Dr Roberts explained.

Because of its anti-inflammatory properties, aspirin might mitigate the risk of developing bile duct cancer by suppressing inflammation through inhibition of the cyclooxygenase pathway, which is known to promote inflammation, he added.

Other studies have shown that aspirin blocks additional cell-signaling cascades that also promote cancer.

"Evidence has been accumulating that regular, long-term use of aspirin is associated with a decreased risk of a number of different cancer types, particularly gastrointestinal cancers," Dr Roberts observed. However, confirmatory studies are needed before aspirin can be routinely recommended to prevent bile duct cancer, he added.

Risk Factors for CCA

Investigators also explored the potential association between a wide variety of risk factors and the development of each of the three CCA subtypes.

The most significant risk factor for CCA was primary sclerosing cholangitis (PSC), which increased the risk for CCA 171.2-fold, at an AOR of 171.2.

This was followed by biliary tract diseases, at an AOR of 12.1, and non-PSC-related cirrhosis, at an AOR of 10.8 (for each, P < .001).

Hepatitis B infection, diabetes, and smoking were each associated with a different magnitude of risk for the three CCA subtypes, "supporting the hypothesis that the three CCA subtypes are distinct diseases and that each subtype has its own susceptibility to risk factors," the authors write.

The authors have disclosed no relevant financial relationships.

Hepatology. Published online April 19, 2016. Abstract


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