Cancer is a leading cause of death in Japan. Several reports indicate that regular aspirin use reduces the incidence and mortality of cancer. Most of these studies, however, were conducted in Western populations. In this study, we explored the effects of aspirin on cancer incidence and mortality in the elderly Japanese.

The Japanese Primary Prevention Project was a multicenter, open-label, randomized, parallel-group trial. Patients (N = 14,601) were aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus. The patients were recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007. We randomized the patients to receive aspirin (n=7297) or not (n=7304), and followed them for up to 6.5 years with the last follow-up exam in May 2012. The primary outcome was a composite of death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal myocardial infarction (Ikeda, et al. JAMA2014). Secondary endpoints included cause-specific mortality and the occurrence of cancer was collected as adverse event. We analyzed the incidence and mortality of newly diagnosed cancer in this population to evaluate the effect of aspirin on cancer in the Japanese.

The cumulative incidence was estimated using the Kaplan-Meier method for each group. The difference between study arms was tested by log-rank test and the hazard ratio was estimated using the Cox proportional model. The time dependency for the hazard ratio was evaluated using both a quantitative assessment of the Cox model, which included an effect of log(time), and examination of a log-minus-log plot.

Cancer was newly diagnosed in 354 (aspirin) and 283 (non-aspirin) patients, and cumulative incidence of newly diagnosed cancer was 5.666% (4.731-6.780%) and 4.194% (3.718-4.731%), respectively (Figure 1). In the aspirin arm, the hazard ratio for newly diagnosed cancer was 1.242 (1.058-1.458) and the incidence of newly diagnosed cancer was significantly higher than in the non-aspirin arm. Colorectal cancer (66 [aspirin] and 50 [non-aspirin]) was most often diagnosed in the study population, followed by stomach (55 and 49, respectively) and lung cancer (56 and 37, respectively). Death related to newly diagnosed cancer occurred in 134 (aspirin) and 125 (non-aspirin) patients, and cumulative mortality was 2.325% (1.907-2.834%) and 2.532% (2.021-3.170%), respectively; the difference was not statistically significant (Figure 2). Furthermore, the Cox proportional model suggested that the cancer incidence in the aspirin arm would decrease to less than that in the non-aspirin arm after the study period (Figure 3).

Contrary to previous studies, this study did not show preventive effects of aspirin on cancer incidence or mortality during the study period. The median follow-up period in in our study was 5.02 years, which was shorter than those of previous reports. Hemorrhagic complications, especially gastro-intestinal bleeding that encouraged the physicians to perform thorough examinations to identify the cause, occurred more often in the aspirin treatment arm, which might have resulted in the earlier diagnosis of cancer and increased the incidence of newly-diagnosed cancer in the aspirin arm. Although the incidence of cancer was higher in the aspirin arm, the mortality related to cancer was not different in each arm. Together, these findings suggest that the higher incidence of cancer was not caused by a carcinogenic effect of aspirin in this population. In conclusion, low-dose aspirin for 5 years did not reduce cancer incidence or mortality in elderly Japanese during the study period.


Off Label Use: aspirin for primary prevention of thrombosis. Teramoto:Bayer: Honoraria. Shimada:Bayer: Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.