December 4, 2019Holli A. Loomans-Kropp, PhD, MPH1,2;
Paul Pinsky, PhD3; Yin Cao, ScD, MPH4; et al Andrew T. Chan, MD, MPH5,6,7,8;
Asad Umar, PhD, DVM2
Author Affiliations Article Information
1Cancer Prevention Fellowship Program, Division of
Cancer Prevention, National Cancer Institute, Rockville, Maryland
2Gastrointestinal and Other Cancers Branch, Division of
Cancer Prevention, National Cancer Institute, Rockville, Maryland
3Early Detection Research Branch, Division of Cancer
Prevention, National Cancer Institute, Rockville, Maryland
4Siteman Cancer Center, Division of Public Health
Sciences, Department of Surgery, Washington University School of Medicine in St
Louis, St Louis, Missouri
5Clinical and Translational Epidemiology Unit,
Massachusetts General Hospital, Harvard Medical School, Boston
6Division of Gastroenterology, Massachusetts General
Hospital, Boston
7Channing Division of Network Medicine, Department of
Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston,
Massachusetts
8Department of Immunology and Infectious Diseases,
Harvard T.H. Chan School of Public Health, Boston, Massachusetts
JAMA Netw Open. 2019;2(12):e1916729. doi:10.1001/jamanetworkopen.2019.16729
Key Points
español 中文 (chinese)
Question Is
aspirin use associated with reduced risk of mortality in older adults?
Findings This
cohort study included 146 152 individuals from the Prostate, Lung, Colorectal,
and Ovarian Cancer Screening Trial and found that aspirin use 3 or more times
per week was associated with reduced risk of all-cause, cancer,
gastrointestinal cancer, and colorectal cancer mortality.
Meaning These
findings suggest that prophylactic aspirin use may reduce risk of mortality
among older individuals.
Abstract
Importance Aspirin
use has been associated with reduced risk of cancer mortality, particularly of
the colorectum. However, aspirin efficacy may be influenced by biological
characteristics, such as obesity and age. With the increasing prevalence of
obesity and conflicting data regarding the effect of aspirin in older adults,
understanding the potential association of aspirin use with cancer mortality
according to body mass index (BMI) and age is imperative.
Objectives To
investigate the association of aspirin use with risk of all-cause, any cancer,
gastrointestinal (GI) cancer, and colorectal cancer (CRC) mortality among older
adults and to perform an exploratory analysis of the association of aspirin use
with mortality stratified by BMI.
Design, Setting, Participants
This cohort study evaluated aspirin use
among participants aged 65 years and older in the Prostate, Lung, Colorectal,
and Ovarian (PLCO) Cancer Screening Trial at baseline (November 8, 1993, to
July 2, 2001) and follow-up (2006-2008). Analysis began in late 2018 and was
completed in September 2019.
Main Outcomes and Measures
All-cause, any cancer, GI cancer, or CRC
mortality. Multivariable hazard ratios (HRs) and 95% CIs were calculated using
time-varying Cox proportional hazards regression modeling, adjusting for
additional factors.
Results A
total of 146 152 individuals (mean [SD] age at baseline, 66.3 [2.4] years;
74 742 [51.1%] women; 129 446 [88.6%] non-Hispanic white) were included in
analysis. The median (interquartile range) follow-up time was 12.5 (8.7-16.4)
years, encompassing 1 822 164 person-years. Compared with no use, aspirin use 1
to 3 times per month was associated with reduced risk of all-cause mortality
(HR, 0.84; 95% CI, 0.80-0.88; P < .001)
and cancer mortality (HR, 0.87; 95% CI,
0.81-0.94; P < .001).
Aspirin use 3 or more times per week was
associated with decreased risk of mortality of all causes (HR, 0.81; 95% CI,
0.80-0.83; P < .001),
any cancer (HR, 0.85; 95% CI, 0.81-0.88;
P < .001),
GI cancer (HR, 0.75; 95% CI, 0.66-0.84;
P < .001),
and CRC (HR, 0.71; 95% CI, 0.61-0.84;
P < .001).
When stratified by BMI (calculated as
weight in kilograms divided by height in meters squared), aspirin use 3 or more
times per week among individuals with BMI 20 to 24.9 was associated with
reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.78-0.85;
P < .001)
and any cancer mortality (HR, 0.86; 95%
CI, 0.79-0.92; P < .001).
Among individuals with BMI 25 to 29.9,
aspirin use 3 or more times per week was associated with reduced risk of
all-cause mortality (HR, 0.82; 95% CI, 0.79-0.85; P < .001), any cancer mortality (HR, 0.86; 95% CI, 0.81-0.91; P < .001), GI cancer mortality (HR, 0.72; 95% CI, 0.60-0.86; P < .001), and CRC mortality (HR, 0.66; 95% CI, 0.51-0.85; P = .001).
Conclusions and Relevance
In this cohort study, aspirin use 3 or
more times per week was associated with a reduction in all-cause, cancer, GI
cancer and CRC mortality in older adults.
Introduction
Aspirin use of 10 years or more is estimated to reduce
cancer incidence and mortality.1-4 Across epidemiological studies, the most significant
reductions in risk have been noted in gastrointestinal (GI) cancers.2,4 Notably, results from the NIH-AARP study,5 the Nurses’ Health Study,6 and Health Professionals Follow-up Study7,8 demonstrated that long-term regular aspirin use was
associated with reduced risk of obesity- and inflammation-associated cancers,
particularly colorectal cancer (CRC). This result has been additionally
illustrated in a 2010 meta-analysis of randomized clinical trials.4 The association of aspirin with reduced cancer
incidence and mortality has been consistently robust among GI cancers; however,
there is limited evidence suggesting that aspirin use is associated with
reduced mortality risk among other cancer types.3,9-11
The US Preventive Services Task Force
(USPSTF) recommends low-dose aspirin use for the prevention of cardiovascular
disease and CRC among average-risk individuals aged 50 to 59 years with a 10%
or greater 10-year risk of cardiovascular disease; however, individuals aged 60
to 69 years should have an individualized approach, while evidence for use
among individuals 70 years and older remains insufficient.12
It is important to note that a 2015
systematic review of the literature by the USPSTF11 found that individuals
with daily aspirin dosing up to 1200 mg for a duration of 4 or more years
exhibited a significant reduction in all-cause and cancer mortality,
demonstrating a similar benefit of low-dose and standard aspirin.
Recently, the results of the Aspirin in Reducing
Events in the Elderly (ASPREE) study13 drew further attention of
the potential cancer preventive effect of aspirin. The ASPREE study was a
randomized clinical trial conducted in the United States and Australia
investigating the efficacy of 100 mg of aspirin daily vs placebo in extending
disability-free survival among elderly individuals (recruitment age 65 years or
70 years) during 4.7 years of follow-up.13
Unexpectedly, an increased risk of
all-cause and cancer-related death was observed in the group randomized to
aspirin.14
Thus, based on the results of the ASPREE randomized
clinical trial that conflict with the preponderance of data showing a benefit
of aspirin use, we examined the association of aspirin use with mortality risk
among older adults enrolled in the Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial. In addition, given data suggesting that aspirin
may be less effective among individuals who are overweight or obese, we
conducted exploratory analyses stratified by body mass index (BMI), calculated
as weight in kilograms divided by height in meters squared.1
Methods
This study is a post hoc analysis of PLCO study data.
The original trial was approved by the institutional review boards at all study
sites (University of Alabama at Birmingham, Georgetown University, University
of Pittsburgh, Washington University in St. Louis, University of Utah,
University of Colorado, University of Minnesota, Pacific Health Research and
Education Institute, Henry Ford Health System, and Marshfield Clinic Research
Foundation). All enrolled participants provided written informed consent. The
use of their data for additional studies and analysis was included in the
original informed consent. This study adhered to the Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE) reporting
guideline.
Study Design
The design and methods of the PLCO Cancer Screening
Trial have been previously described.15,16
Briefly, participants aged 55 to 74 years
were randomized to the intervention (screening) or control arm at 10 screening
centers in the United States between November 8, 1993, and July 2, 2001.
Pertinent exclusion criteria for this study were individuals with a history of
CRC or lung, prostate, or ovarian cancer, previous surgical removal of the
colon, lung, or prostate, or, starting in 1995, individuals who had a
colonoscopy, sigmoidoscopy, or barium enema in the 3 years prior to study
randomization. This cohort included participants who were 65 years or older or
survived until age 65, had a valid baseline questionnaire (BQ) after study
enrollment, and had reported information on aspirin use at baseline. Completion
of a follow-up supplemental questionnaire (SQ) by participants between 2006 and
2008 was not required for inclusion into the study cohort. All responses to the
BQ and SQ were ascertained by self-report. The full content of both
questionnaires has been published previously.17,18
Briefly, the BQ asked, “During the last
12 months, have you regularly used aspirin or aspirin-containing products, such
as Bayer, Bufferin, or Anacin (Please do not include aspirin-free products such
as Tylenol and Panadol).” If the respondent answered yes, the frequency
categories were given as less than 2 per month, 2 to 3 per month, 1 per week, 2
per week, 3 to 4 per week, 1 per day, or 2 or more per day. The SQ asked,
“During the last 12 months, about how often did you usually take aspirin (examples
of aspirin include Bayer, Bufferin, Anacin, and baby aspirin)?” The frequency
categories were given as none or less than once per month, 1 to 3 times per
month, 1 to 2 times per week, 3 to 6 times per week, and 7 or more times per
week. To allow for consistent values between BQs and SQs, we collapsed the
aspirin use frequency variables into no aspirin use or less than once per
month, 1 to 3 times per month, 1 to 2 times per week, and 3 or more times per
week. Usual dose information was not available on the BQ; therefore, this
analysis does not consider dose. We categorized BMI as less than 20, 20 to
24.9, 25 to 29.9, and 30 or higher.
Initial analysis of the PLCO Cancer Screening Trial
was completed after 13 years of follow-up or on December 31, 2009, whichever
came first.15
Deaths were ascertained via annual study
update questionnaire, individual reports, or death certificates. Beginning in
2011, participants were reconsented for follow-up. This allowed for linkage to
the National Death Index, which extended mortality follow-up for up to 20 years
after randomization.19
For those reconsenting, the end of
mortality follow-up was December 31, 2015 or their date of death, whichever
came first. For the approximately 15% of individuals who were alive in 2011 but
who declined extended follow-up, the end of mortality follow-up was their
declining date, which was generally in 2011.
Statistical Analysis
The purpose of this analysis was to assess the
associations among aspirin use, BMI, and mortality of all causes, any cancer,
gastrointestinal (GI) cancer, and CRC among individuals in the PLCO Cancer
Screening Trial who survived to age 65 years and older (Figure 1). Participant
follow-up time was measured from the time of cohort entry, which was either the
date of PLCO Cancer Screening Trial enrollment or age 65 years, whichever
occurred last, until the date of death or December 31, 2015, whichever came first.
Survival time was measured from the time of cohort entry, until time of death
of any cause. Hazard ratios (HRs) were calculated using Cox proportional
hazards regression models to analyze the associations among aspirin use (no
use, 1-3 times per month, 1-2 times per week, and ≥3 times per week), BMI
(<20, 20-24.9, 25-29.9, ≥30), and
mortality, controlling for covariates. As aspirin use, BMI, and other
covariates may have changed between completion of the BQ and SQ, time-varying
proportional hazards models were used. Initial aspirin use and covariate values
were taken from the BQ for participants 65 years or older at randomization and
for participants younger than 65 years at randomization who either did not fill
out the SQ or filled it out after reaching age 65 years; initial values were
taken from the SQ for those younger than 65 years at randomization completing
the SQ before age 65 years. Among those with initial aspirin use and covariate
values taken from the BQ and who also completed the SQ, values were updated at
that time to the corresponding SQ values. Time-varying variables included in
the model were aspirin use, BMI, smoking status (ie, never, current, or former
smoker), history of myocardial infarction, history of stroke, history of
hypertension, history of diabetes, and ibuprofen use 3 or more times per week.
Static variables included in the models were sex (male or female),
race/ethnicity (white non-Hispanic, black non-Hispanic, or other), and
randomization arm (intervention or control). We additionally stratified by BMI
to evaluate the association of aspirin use and BMI with mortality.
Finally, as an exploratory assessment of longitudinal
patterns of aspirin use, we examined risk of mortality only among participants
who had completed aspirin frequency questions on the BQ and SQ. Follow-up for
this cohort subset began at age 65 years or completion of the SQ, whichever
occurred last. Participants were categorized according to baseline and
follow-up aspirin use as (1) consistent nonusers (use
>1 time per week or no use at baseline
and follow-up), (2) users at baseline only (use ≥1 time per week at baseline
only), (3) users at follow-up only (use ≥1 time per week at follow-up only), or
(4) consistent users (use ≥1 time per week at baseline and follow-up). We used
weekly aspirin use as our metric in this analysis for consistency with previous
analyses and to include the maximum number of participants with BQ and SQ data.
Supplemental questionnaire variables included in the model were randomization
arm, sex (male or female), race/ethnicity (white non-Hispanic, black
non-Hispanic, or other), BMI, smoking status (never, current, or former
smoker), history of myocardial infarction, history of stroke, history of
hypertension, history of diabetes, and ibuprofen use 3 or more times per week.
Causes of death were determined by International Classification of Diseases, Ninth
Revision (ICD-9)
codes.20
All-cause mortality was defined as a
reported death of any cause. Any cancer mortality was defined as a reported
cause of death by cancer based on the official PLCO Cancer Screening Trial
definitions, derived from standard ICD-9 groupings. Cause of death by GI cancer was determined
by ICD-9 codes for esophagus (150), gastric (151), and colorectal
(153 and 154) cancer, whereas CRC was determined by ICD-9 codes for CRC only (153 and 154). All statistical
analyses were performed in SAS statistical software version 9.4 (SAS Institute).
P values
were 2-tailed, and statistical significance was set at less than .05.
Results
The eligibility criteria for the study analysis are
outlined in Figure 1. After excluding individuals who died before age 65 years, there were
146 152 participants (mean [SD] age at baseline, 66.3 [2.4] years; 74 742
[51.1%] women; 129 446 [88.6%] non-Hispanic white) included in our analysis.
The mean (SD) duration from baseline to completing the SQ was 9.1 (1.9) years
and the median (range) was 9.2 (4.6-14.2) years, with a median (interquartile
range) follow-up time of 12.5 8.7-16.4) years. Among the total cohort included
in our study, 40 419 individuals (27.7%) died during follow-up, including
12 421 individuals (30.7%) who died of any cancer, 1425 individuals (3.5%) who
died of GI cancers (including 353 individuals with esophageal cancer [2.8%] and
258 individuals with gastric cancer [2.1%]), and 814 individuals (6.6%) who
died of CRC. Demographic characteristics of the cohort are summarized in Table 1.
The results of the Cox proportional hazards regression
model are presented in Table 2. In our model, any aspirin use was associated with reduced all-cause and
cancer-specific mortality. Reduced risk of all-cause mortality was associated
with using aspirin 1 to 3 times per month (HR, 0.84; 95% CI, 0.80-0.88;
P < .001),
1 to 2 times per week (HR, 0.86; 95% CI,
0.81-0.90; P < .001),
or 3 or more times per week (HR, 0.81;
95% CI, 0.80-0.83; P < .001).
A similar association was noted for risk
of cancer mortality and aspirin use 1 to 3 times per month (HR, 0.87; 95% CI,
0.81-0.94; P < .001)
or 3 or more times per week (HR, 0.85;
95% CI, 0.81-0.88; P < .001).
Use of aspirin 3 or more times per week
was also associated with significantly reduced risk of GI cancer mortality (HR,
0.75; 95% CI, 0.66-0.84; P < .001)
and CRC mortality (HR, 0.71; 95% CI,
0.61-0.84; P < .001).
Data for the additional covariates
included in the model are provided in the eTable in the Supplement.
To explore the potential association of aspirin use
and BMI with mortality risk, we stratified the cohort according to BMI. The
results are shown in Figure 2. Compared with no aspirin use and among individuals with a BMI of 20 or
higher, aspirin use was associated with reduced risk of all-cause mortality
when used 1 to 3 times per month (BMI 20-24.9: HR, 0.83; 95% CI, 0.76-0.89;
P < .001;
BMI 25-29.9: HR, 0.82; 95% CI, 0.78-0.93;
P < .001;
BMI ≥30: HR, 0.85; 95% CI, 0.78-0.93;
P < .001),
1 to 2 times per week (BMI 20-24.9: HR,
0.85; 95% CI, 0.77-0.94; P = .002;
BMI 25-29.9: HR, 0.85; 95% CI, 0.78-0.93;
P = .001;
BMI ≥30: HR, 0.86; 95% CI, 0.76-0.96;
P = .01),
or 3 or more times per week (BMI 20-24.9:
HR, 0.82; 95% CI, 0.78-0.85; P < .001;
BMI 25-29.9: HR, 0.82; 95% CI, 0.79-0.85;
P < .001;
BMI ≥30: HR, 0.78; 95% CI, 0.75-0.82;
P < .001)
(Figure 2A).
Reduced risk of cancer-specific mortality was noted among individuals with
reported aspirin use 3 or more times per month and BMI 20 to 24.9 (HR, 0.86;
95% CI, 0.79-0.92; P < .001),
BMI 25-29.9 (HR, 0.86; 95% CI, 0.81-0.91;
P < .001)
or BMI 30 or higher (HR, 0.81; 95% CI,
0.75-0.88; P < .001)
(Figure 2B).
No statistically significant risk reduction was observed for cancer mortality
among participants who used aspirin 1 to 2 times per week or 1 to 3 times per
month, except for aspirin use 1 to 3 times per month among individuals with BMI
20 to 24.9 (HR, 0.83; 95% CI, 0.72-0.95; P = .007) (Figure 2B).
Individuals with BMI 25 to 29.9 who
used aspirin 3 or more times per week were associated with reduced risk of GI
cancer mortality (HR, 0.72; 95% CI, 0.60-0.86; P < .001) and CRC mortality (HR, 0.66; 95% CI, 0.51-0.85; P < .001) (Figure 2C
and D).
We additionally examined the association between
reported aspirin use at baseline and at the time of the SQ with risk of
mortality. Participants who had reported aspirin use at follow-up only or
consistent users were associated with a reduced risk of mortality
(Table 3). Individuals
who reported aspirin use at follow-up only were associated with reduced risk of
all-cause mortality (HR, 0.79; 95% CI, 0.76-0.82; P < .001), cancer mortality (HR, 0.82; 95% CI, 0.76-0.88; P < .001), and GI cancer mortality (HR, 0.74; 95% CI, 0.59-0.94;
P = .01).
Individuals who were consistent aspirin
users were also associated with reduced risk of all-cause mortality (HR, 0.80;
95% CI, 0.76-0.83; P < .001),
cancer mortality (HR, 0.77; 95% CI,
0.72-0.83; P < .001),
and GI cancer mortality (HR, 0.75; 95%
CI, 0.59-0.94; P = .01).
Of particular interest, the HRs for
CRC-associated mortality were 0.88 (95% CI, 0.58-1.33; P = .53) for
users at baseline only, 0.62 (95% CI, 0.46-0.85; P = .003) for users at follow-up only, and 0.62 (95% CI, 0.46-0.85;
P = .003)
for consistent users, compared with
nonusers of aspirin.
Discussion
This cohort study found that aspirin use among
individuals 65 years and older was associated with a lower risk of mortality.
This observation was consistent across all causes of mortality (ie, all-cause,
cancer, GI cancer, and CRC); however, the greatest reduction in risk was noted
for CRC mortality among individuals who used aspirin 3 or more times per week.
Additionally, our exploratory analyses investigating the potential associations
among aspirin use, BMI, and mortality risk suggest that the efficacy of aspirin
as a cancer preventive agent may be associated with BMI. Participants in the
PLCO Cancer Screening Trial who were underweight (ie, BMI
<20) had no observable benefit
associated with aspirin use, while those with BMI 20 or higher were associated
with reduced mortality risk, particularly with aspirin use 3 or more times per
week. reduced risk of CRC mortality was only associated with individuals with
BMI 20 to 29.9 who reported aspirin use 3 or more times per week.
The efficacy of prophylactic aspirin use for
prevention of cancer incidence and mortality has been debated; however, the
most evidence from prospective cohorts and secondary analyses from clinical
trials indicates a protective association with aspirin use. A 2016 systematic
analysis of primary and secondary cardiovascular prevention trials21 found reduced CRC
incidence 10 to 19 years after aspirin use initiation. This association
persists among investigations of aspirin use and cancer mortality. A 2011
systematic analysis of 8 clinical trials22 found that daily aspirin
use was associated with reduced risk of death of several cancers, with
increased benefit associated with long-term use. A similar association was
observed in a 2018 cohort study23 of veterans in which
aspirin users were associated with reduced risk of CRC mortality compared with
nonusers. This association was additionally examined in the Cancer Prevention
Study-II Nutrition Cohort,24
in which daily aspirin use was associated
with reduced overall cancer mortality. These observations are in contrast with
data from the ASPREE trial.13
However, the interpretation of the ASPREE
results is limited owing a lack of an association of aspirin with cancer and
CRC incidence and the short duration of follow-up.25
With additional follow-up, an association
of aspirin with lower cancer incidence and death may have emerged.26
In addition, a 2018 combined analysis of
the NIH-AARP Diet and Health Study and the PLCO Cancer Screening Trial27 reported decreased risk
of all-cause, cancer, and cardiovascular mortality associated with daily
aspirin use. However, a dosage that exceeded 1 per day was associated with an
increased risk of mortality. These data also did not account for effect modifications
by BMI on mortality risk. Previous studies have also found that variables, such
as BMI, are associated with the efficacy of prophylactic aspirin. In a 2012
study of the Cancer Prevention Study-II Nutrition Cohort,28
individuals with prediagnostic BMI 30 or
higher were associated with increased risk of all-cause and CRC death. A
similar association was demonstrated across several other cohort and
case-control studies, cancers, and causes of death.27,29-31
The observation that BMI may be associated with
efficacy of aspirin in individuals 65 years and older is notable; however, our
findings require further confirmation. Increasing rates of overweight and
obesity globally may substantially alter the population-based efficacy of
cancer prevention prophylatics.32
Studies have suggested that aspirin has
reduced effectiveness as a primary prevention modality among individuals who
are obese owing to decreased bioavailability and antithrombotic efficacy;
however, this study did not find an association of overweight or obesity with
decreased efficacy.5,33-35
Therefore, although aspirin use is
associated with benefit as a cancer preventive agent, the changing
characteristics of the global population may alter its efficacy and must be
considered along with age and risk of bleeding before recommending aspirin for
cancer prevention.
Limitations and Strengths
Our study has several limitations. First, this is a
secondary analysis of a randomized intervention (screening) trial with
self-reported data on aspirin use. When collecting self-reported data, one must
be aware of the limitations to these data, such as underreporting parameters of
interest and the potential effect of this error in the analyses, such as
biasing toward the null. For example, it is possible that aspirin use was
underreported if the participant was unaware that a given agent, based upon its
trade name, was classified as aspirin. Next, the information on aspirin use may
be subject to participant interpretation and measurement error. Regular use of
aspirin was not defined in the BQ, so participants could then have interpreted
regular aspirin use differently, which may have affected their categorization
(eg, none, monthly, weekly, daily). Furthermore, the information collected
regarding aspirin dosage was limited. These issues may, in addition to
confounding by unmeasured covariates, help explain the lack of a dose-response
association for mortality risk in the observed data. Though there is
substantial evidence documenting the association of frequent aspirin use with
cancer prevention, the biological effect of low frequency use (eg, 1-3 times
per month) is uncertain. Therefore, the noted risk reduction associated with
this group may be due to unmeasured confounders. Along similar lines, it
remains possible that individuals who reported low or no use of aspirin were
unable to tolerate aspirin use for an extended length of time, perhaps owing to
risk of bleeding or gastrointestinal injury, and may be inherently different
than those who reported aspirin use.36
Additionally, our analysis was focused on
individuals in the PLCO Cancer Screening Trial cohort who survived to and began
follow-up at or after age 65 years. However, only a small percentage (5.5%) of
the PLCO cohort was ineligible for our study.
Although this study had several limitations, the
research questions investigated examining the associations among aspirin use,
BMI, and mortality adds to our knowledge of modifiable factors associated with
cancer prevention efficacy. We were able to explore this question in a large,
prospective study with an extended follow-up period.
Conclusions
In this cohort study, we found a significant
association of aspirin use with reduced all-cause, any cancer, GI cancer, and
CRC mortality among individuals 65 years and older in the PLCO Cancer Screening
Trial. Aspirin use was associated with reduced risk of all-cause and any cancer
mortality, and aspirin use 3 or more times per week was associated with reduced
risk of GI cancer mortality and CRC mortality when stratified by BMI. Future
studies should further examine the association of BMI with the efficacy of
aspirin as a cancer preventive agent to adapt to the changing global obesity
trends.
Article Information
Accepted for Publication: October 14, 2019.
Correction: This
article was corrected on January 17, 2020, to fix a data error in the Results section
of the Abstract.
Open Access: This
is an open access article distributed under the terms of the CC-BY License. © 2019 Loomans-Kropp HA et al. JAMA Network Open.
Corresponding Author: Holli A. Loomans-Kropp, PhD, MPH, Division of Cancer
Prevention, National Cancer Institute, 9609 Medical Center Dr, Room 5E232,
Rockville, MD, 20850 (holli.loomans@nih.gov).
Author Contributions: Drs Loomans-Kropp and Pinsky had full access to all of
the data in the study and take responsibility for the integrity of the data and
the accuracy of the data analysis.
Concept and design: Loomans-Kropp, Umar.
Acquisition, analysis, or interpretation of data:
Loomans-Kropp, Pinsky, Cao, Chan.
Drafting of the manuscript: Loomans-Kropp.
Critical revision of the manuscript for important
intellectual content: All
authors.
Statistical analysis: Loomans-Kropp, Pinsky, Chan.
Administrative, technical, or material support:
Umar.
Supervision: Chan,
Umar.
Conflict of Interest Disclosures: Dr Chan reported receiving grants and personal fees
from Bayer Pharma AG, personal fees from Pfizer Janssen Pharmaceuticals, and
support from the Stuart and Suzanne Steele MGH Research Scholarship outside the
submitted work. No other disclosures were reported.
Funding/Support: This study was funded by grants from the National
Cancer Institute (Dr Cao: K07CA218377; Dr Chan: R01-CA137178) and the Stuart
and Suzanne Steele MGH Research Scholarship (Dr Chan).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data;
preparation, review, or approval of the manuscript; and decision to submit the
manuscript for publication.
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