Abstract 876: Long-term use of aspirin and risk of cancer
Authors: Cao Yin , Nishihara Reiko , Wu Kana , Wang Molin , Ogino Shuji , Spiegelman Donna , Fuchs Charles S. , Giovannucci Edward L. , Chan Andrew T. 
Published: August 2015

Abstract
Background: Post-hoc analyses of RCTs of aspirin for the prevention of cardiovascular disease support a potential role of daily aspirin use, primary low-dose aspirin, in reducing overall cancer incidence. However, long-term follow-up of the largest RCT of aspirin, the Women's Health Study, found a reduction only in risk of colorectal cancer but not overall cancer with alternate-day low-dose aspirin. Uncertainties remain in relation to the optimum dose, duration of use, the impact of discontinuing use, as well as potential differential benefits within subgroups.
Methods: We prospectively followed 82,600 female nurses and 47,651 male health professionals enrolled in the Nurses’ Health Study (1980) and Health Professionals Follow-up Study (1986) until June 2012 and January 2010, respectively. Biennially, we collected data on aspirin use, other risk factors, and diagnoses of cancer. Cox proportional hazards models with time varying covariates were used to estimate RRs and 95% confidence intervals (95% CIs).
Results: During up to 32 years of follow-up, we documented 27,985 (20,414 among women, 7,571 among men [excluding non-advanced prostate cancer]) incident cancers over 3,137,359 person-years. Compared with non-regular users, regular aspirin use (≥2 standard [325-mg] tablets per week in women; ≥2 times per week in men) was associated with lower risk of overall cancer (multivariable RR 0.95; 95% CI 0.93-0.98), which was primarily due to a lower incidence of gastrointestinal (GI) cancers (HR 0.80; 95% CI 0.75-0.85), including colorectal cancer (HR 0.75; 95% CI 0.69-0.81) and gastroesophageal cancers (HR 0.86; 95% CI 0.71-1.04). Regular use of aspirin was not associated with risk of non-GI cancer (HR 0.98; 95% CI 0.96-1.01). In particular, no link between aspirin and breast cancer, advanced prostate cancer or lung cancer was identified. The benefit of aspirin on overall cancer appeared to be dose-dependent: compared with participants reported no aspirin use, the RRs for cancer were 0.99 (95% CI 0.95-1.03) for those who used 0.5 to 1.5 standard aspirin tablets per week, 0.97 (95% CI 0.93-1.01) for 2 to 5 aspirin per week, 0.93 (95% CI, 0.89-0.97) for 6 to 14 aspirin per week, and 0.94 (95% CI, 0.87-1.00) for ≥15 aspirin per week (P for trend &lt;0.001). Significant risk reduction required at least 16 years of use (P for trend = 0.001) and was no longer evident within 4 years of discontinuing use. The association of aspirin use with cancer risk was similar for women and men and did not vary by race, history of diabetes, family history of cancer, body mass index, smoking history, regular NSAID and multivitamin use.
Conclusion: Our results support an association of regular aspirin use with modestly reduced incidence of overall cancer. However, in contrast to the findings in the post-hoc analyses of several cardiovascular RCTs, higher doses of aspirin may be required to achieve benefits in cancer prevention. Longer duration of use was strongly associated with lower risk.
Citation Format: Yin Cao, Reiko Nishihara, Kana Wu, Molin Wang, Shuji Ogino, Donna Spiegelman, Charles S. Fuchs, Edward L. Giovannucci, Andrew T. Chan. Long-term use of aspirin and risk of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 876. doi:10.1158/1538-7445.AM2015-876