Regular Aspirin Use and Reduction in Risk for Hepatocellular Carcinoma
A pooled analysis of two large U.S. prospective cohort studies reported in JAMA Oncology by Simon et al indicates that regular use of aspirin is associated with a significant reduction in risk for hepatocellular carcinoma (HCC), with an apparent dose- and duration-dependent effect.
Study Details
The study involved data from 133,371 participants, including 87,507 women and 45,864 men, in the Nurses’ Health Study and Health Professional Follow-up Study who reported on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men. Participants with cancer diagnosis at baseline other then nonmelanoma skin cancer were excluded from analysis. In 1996, the median time of follow-up, mean age was 62 years for women and 64 years for men. The results shown are from a multivariate model that was conditioned on age (continuous years) and year of questionnaire return, and adjusted for sex, race/ethnicity, body mass index, alcohol intake, smoking status, physical activity, diabetes, hypertension, dyslipidemia, regular multivitamin use, regular use of oral antidiabetic medications, and regular use of statins, as well as regular use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) assessed as a time-varying covariate.
Aspirin Use and HCC Risk
Over more than 26 years of follow-up representing 4,232,188 person-years, 108 participants were diagnosed with HCC, including 65 women and 43 men. Compared with nonregular use (no use or < 2 standard-dose 325-mg tablets per week), regular aspirin use, defined as ≥ 2 standard-dose tablets per week, was associated with a significantly reduced risk of HCC (adjusted hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34–0.77). Compared with nonuse, adjusted hazard ratios for HCC were 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 > 1.5–5 tablets per week, and 0.49 (95% CI = 0.28–0.96) for > 5 tablets per week (P for trend = .006).
The association between aspirin dose and HCC risk remained significant (P for trend = .005) after additional adjustment for duration of aspirin use. No reduction in HCC risk was observed with < 5 years of regular aspirin use vs nonregular use; adjusted HRs were 0.62 (95% CI = 0.34–1.13) for 5 to < 10 years of use and 0.55 (95% CI = 0.32–0.93) for ≥ 10 years of use (P for trend = .03). Analysis of dose and duration indicated that the benefit of aspirin in reducing HCC risk was apparent with use of 1.5 or more standard-dose aspirin tablets per week for ≥ 5 years (adjusted HR = 0.41, 95% CI = 0.21–0.77). Compared with current aspirin users, increased number of years since discontinuation of use was associated with increased HCC risk (P for trend = .006); the HR for discontinuation ≥ 8 years ago vs current use was 1.77 (95% CI = 1.06–2.97).
Use of nonaspirin NSAIDs was not associated with HCC risk (adjusted HR = 1.09, 95% CI = 0.78–1.51).
The investigators concluded, “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.”
The study was supported by grants from the National Cancer Institute and National Institutes of Health.
Andrew T. Chan, MD, MPH, of the Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, is the corresponding author for the JAMA Oncology article.
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