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JAMA Oncol. 2018 Dec 1;4(12):1683-1690. doi: 10.1001/jamaoncol.2018.4154.

Association Between Aspirin Use and Risk of Hepatocellular Carcinoma.

Simon TG1,2,3, Ma Y4,5, Ludvigsson JF6,7,8, Chong DQ9, Giovannucci EL5,10,11, Fuchs CS12, Meyerhardt JA13, Corey KE1,2,4, Chung RT1,2, Zhang X5, Chan AT2,3,5,14,15.

Author information

Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.
Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
Columbia University College of Physicians and Surgeons, New York, New York.
National Cancer Centre Singapore, Singapore.
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Yale University Cancer Center, New Haven, Connecticut.
Dana-Farber Cancer Center, Boston, Massachusetts.
Broad Institute, Boston, Massachusetts.
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.



Prospective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited.


To examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations.

Design, Setting, and Participants:

Pooled analysis of 2 prospective US cohort studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded.

Main Outcomes and Measures:

Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC.


Of the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51).

Conclusions and Relevance:

This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.

[Indexed for MEDLINE]
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