NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

Author(s): Petrick JL,  Sahasrabuddhe VV,  Chan AT,  Alavanja MC,  Beane-Freeman LE,  Buring JE,  Chen J,  Chong DQ,  Freedman ND,  Fuchs CS,  Gaziano JM,  Giovannucci E,  Graubard BI,  Hollenbeck AR,  Hou L,  Jacobs EJ,  King LY,  Koshiol J,  Lee IM,  Linet MS,  Palmer JR,  Purdue MP,  Rosenberg L,  Schairer C,  Sesso HD,  Sigurdson AJ,  Wactawski-Wende J,  Zeleniuch-Jacquotte A,  Campbell PT,  McGlynn KA

Journal: Cancer Prev Res (Phila)

Date: 2015 Dec

Major Program(s) or Research Group(s): BGCRG

PubMed ID: 26391917

PMC ID: PMC4704448

Abstract: Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.