EXPOSURE TO ASBESTOS: A PUTATIVE UNKNOWN RISK FACTOR FOR INTRAHEPATIC CHOLANGIOCARCINOMA

Cholangiocarcinoma (CC) represents the second most frequent primitive liver malignancy, representing about 15% of primary liver tumors in the world. In the last thirty-year period, a progressive increase of incidence and mortality for CC has been reported worldwide and it mainly involves the intrahepatic form (ICC). Some conditions activating chronic inflammatory pathway (primary sclerosing cholangitis [PSC], anatomic abnormalities of biliary tract, hepatic infections, lithiasis) are well recognised as risk factors but they are responsible for only 10% of CC cases. Probably other environmental factors are involved in the remaining 80-90% of cases and asbestos could be one of these. The role of asbestos in development of gastrointestinal tumors has not been assesed but an association between exposure to amphibole fibers and their presence in hepatic tissue has been reported. Objectives: We conducted a case-control analysis to explore the association between occupational exposure to asbestos and CC development. Methods: This study was based on historical data from 155 consecutive patients affected by histologically confirmed cholangiocarcinoma (69 affected by ICC and 86 by extrahepatic cholangiocarcinoma [ECC]) referring to our institution in 2007-2011. When feasible, cases were individually matched (ratio up to 1:4) by calendar period of birth (5-years intervals), sex and provenience to historical populations controls (sampled from studies about carpal tunnel syndrome, renal cell carcinoma and retinal detachment). Occupational exposure to asbestos was assessed by industrial hygienists considering lifetime prevalent job-titles. Separate conditional logistic regression models were conducted for ECC and ICC; estimates were adjusted for smoking status and socioeconomic class. Results: We matched 149 controls to 49 cases of ICC and 212 controls to 59 cases of ECC. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.73, 95%CI 1.54-14.54); conversely, no evidence of increased risk was found for ECC (adjusted OR 1.84, 95%CI 0.66-5.08). Sensitivity analyses conducted using only patients from our city district (Bologna) (conducted to minimize referral bias) produced confirmatory figures (unadjusted OR of ICC 3.67; unadjusted OR of ECC 1.09). Conclusion: Findings from our exploratory study support the hypothesis that ICC could arise from chronic inflammation caused by presence of asbestos fibers. Asbestos was used extensively for over 100 years and, because of the long lag time between exposure and the development of disease, we are now experiencing part of asbestos related disease such as mesothelioma. The relationship between asbestos exposure and cholangiocarcinoma could partially explicate the worldwide increase in ICC incidence.