608 Articles | JNCI Vol. 99, Issue 8 | April 18, 2007
Recently, the Women’s Health Study, a large 10-year randomized
trial of alternate-day low-dose aspirin (100 mg every other day)
showed no reduced risk of any cancer in aspirin users ( 1 ). However,
the potential effect of daily adult-strength aspirin (i.e., ≥ 325 mg/day)
on overall cancer incidence or on incidence of specific individual
cancers remains uncertain. Considerable evidence suggests that
aspirin use could reduce risk of several cancers. Aspirin and other
nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the devel-
opment of many different types of cancers in rodent models,
including cancers of the colorectum, breast, prostate, lung, skin,
and bladder ( 2 ). It has been hypothesized that aspirin may inhibit
carcinogenesis by reducing the synthesis of prostaglandins by cyclo-
oxgenase (COX)-1 and COX-2 enzymes ( 3 ). Aspirin reduced risk of
colorectal polyp recurrence in two randomized trials ( 4 , 5 ) and has
been consistently associated with lower risk of colorectal cancer in
observational studies ( 2 ), although the optimal dose associated with
reduced colorectal cancer risk remains unclear. Meta-analyses of
observational studies have reported considerably reduced risk of
gastric and esophageal cancer with aspirin use ( 6 ), although these
cancers are not common in the United States. Meta-analyses of
observational studies have also reported smaller, but statistically
significant, reductions in risk of breast ( 6 ), prostate ( 7 ), and lung
cancers ( 8 ) with aspirin use, and some studies have also suggested
reduced risk of other cancers ( 9 ).
Although many epidemiologic studies have examined the asso-
ciation between aspirin use and individual cancers, it is diffi cult to
use results of these studies to assess the overall potential cancer
prevention benefi t of any particular aspirin regimen. Studies of
Affiliation of authors: Department of Epidemiology and Surveillance
Research, American Cancer Society, Atlanta, GA .
Correspondence to: Eric J. Jacobs, PhD, Department of Epidemiology and
Surveillance Research, American Cancer Society, National Home Office,
1599 Clifton Rd NE, Atlanta, GA 30329 (e-mail: email@example.com ).
See “Notes” following “References.”
© The Author 2007. Published by Oxford University Press. All rights reserved.
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A Large Cohort Study of Long-Term Daily Use of
Adult-Strength Aspirin and Cancer Incidence
Eric J . Jacobs , Michael J . Thun , Elizabeth B . Bain , Carmen Rodriguez , S. Jane Henley , Eugenia E . Calle
Background Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and
possibly several other cancers, including prostate and breast cancers. Recent results from the Women’s
Health Study randomized trial indicate that long-term use of low-dose aspirin (100 mg every other day)
does not substantially reduce cancer risk. However, the potential effect of long-term daily use of higher
doses of aspirin on cancer incidence remains uncertain.
Methods We examined associations between long-term daily use of adult-strength aspirin ( ≥ 325 mg/day) and both
overall cancer incidence and incidence of 10 types of cancer among 69 810 men and 76 303 women partici-
pating in the Cancer Prevention Study II Nutrition Cohort, a relatively elderly population. Aspirin use was
reported at enrollment in 1992 – 1993 and updated in 1997, 1999, and 2001. Multivariable Cox proportional
hazards regression was used to calculate rate ratios (RRs).
Results During follow-up through June 2003, 10 931 men and 7196 women were diagnosed with cancer. Long-
term ( ≥ 5 years) daily use of adult-strength aspirin, compared with no use, was associated with lower over-
all cancer incidence in men (multivariable-adjusted RR = 0.84, 95% confidence interval [CI] = 0.76 to 0.93)
and non–statistically significantly lower overall cancer incidence in women (multivariable-adjusted
RR = 0.86, 95% CI = 0.73 to 1.03). Overall cancer incidence per 100 000 person-years (standardized to the
age distributions of men and women in the study) with long-term daily aspirin use and no aspirin use was
1858 and 2163, respectively, among men and 1083 and 1169, respectively, among women. Long-term
daily aspirin use was associated with lower incidence of colorectal cancer (RR = 0.68, 95% CI = 0.52 to 0.90
among men and women combined) and prostate cancer (RR = 0.81, 95% CI = 0.70 to 0.94) and a
non–statistically significant lower risk of female breast cancer (RR = 0.83, 95% CI = 0.63 to 1.10).
Conclusions Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer
incidence in populations among whom colorectal, prostate, and breast cancers are common.
J Natl Cancer Inst 2007;99: 608 – 15
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JNCI | Articles 615
(27) Muscat JE , Chen SQ , Richie JP , Altorki NK , Citron M , Olson S , et al .
Risk of lung carcinoma among users of nonsteroidal antiinfl ammatory
drugs . Cancer 2003 ; 97 : 1732 – 6 .
(28) Hayes JH , Anderson KE , Folsom AR . Association between nonsteroidal
anti-infl ammatory drug use and the incidence of lung cancer in the Iowa
women’s health study . Cancer Epidemiol Biomarkers Prev 2006 ; 15 :
2226 – 31 .
We thank Alison Mondul, MSPH, and Kerri Brady, MS, for their assistance
with statistical analyses while they were employees at the American Cancer
Society. The funding agency (i.e., the American Cancer Society) had no role in
the analysis or interpretation of data or in the writing of the manuscript.
Manuscript received September 19 , 2006 ; revised February 5 , 2007 ;
accepted February 27, 2007.
by guest on December 26, 2015