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impact of Obesity on Cancer Survivorship and the Potential
Relevance of Race and ethnicity
Kathryn H. Schmitz, Marian L. Neuhouser, Tanya Agurs-Collins, Krista A. Zanetti, Lisa Cadmus-Bertram, Lorraine T. Dean,
Bettina F . Drake
Manuscript received August 15, 2012; revised July 17 , 2013; accepted July 18, 2013.
Correspondence to: Kathryn H. Schmitz, PhD, University of Pennsylvania, Perelman School of Medicine, 423 Guardian Dr, 8th Fl Blockley Hall, Philadelphia,
PA 19104-6021 (e-mail: email@example.com).
Evidence that obesity is associated with cancer incidence and mortality is compelling. By contrast, the role of obesity in cancer
survival is less well understood. There is inconsistent support for the role of obesity in breast cancer survival, and evidence for
other tumor sites is scant. The variability in findings may be due in part to comorbidities associated with obesity itself rather than
with cancer, but it is also possible that obesity creates a physiological setting that meaningfully alters cancer treatment efficacy. In
addition, the effects of obesity at diagnosis may be distinct from the effects of weight change after diagnosis. Obesity and related
comorbid conditions may also increase risk for common adverse treatment effects, including breast cancer–related lymphedema,
fatigue, poor health–related quality of life, and worse functional health. Racial and ethnic groups with worse cancer survival out-
comes are also the groups for whom obesity and related comorbidities are more prevalent, but findings from the few studies that
have addressed these complexities are inconsistent. We outline a broad theoretical framework for future research to clarify the
specifics of the biological–social–environmental feedback loop for the combined and independent contributions of race, comorbid
conditions, and obesity on cancer survival and adverse treatment effects. If upstream issues related to comorbidities, race, and
ethnicity partly explain the purported link between obesity and cancer survival outcomes, these factors should be among those
on which interventions are focused to reduce the burden of cancer.
J Natl Cancer Inst;2013;105:1344–1354
The prevalence of overweight (body mass index [BMI] = 25.0–
29.9 kg/m2) and obesity (BMI ≥ 30.0 kg/m2) in the United States
rose from 13.5% in the 1960s to 35.9% in 2010 (1,2). Of the top 10
causes of death in the United States in 2009, five are related to obe-
sity, including heart disease, stroke, cancer, diabetes mellitus, and
kidney disease (3). Disparities have been noted in cancer survival
and treatment outcomes across ethnic groups and levels of obesity
(4–6). Herein we review evidence regarding the potential impact of
obesity and race on cancer survival and treatment outcomes.
The recently published “Annual Report to the Nation on the
Status of Cancer” (4) commented that differences in cancer out-
comes across racial and ethnic groups might be explained by dif-
ferences in risk behaviors and access to and use of screening and
cancer treatments. The racial and ethnic groups for whom cancer
survival is worse are the same groups in which obesity is more
prevalent, including blacks and Native American/Pacific Islanders
(1,4). It could be hypothesized that the disparities by race and eth-
nicity for cancer survival and treatment outcomes are explained,
in part, by disparities in obesity and related comorbidities. A theo-
retical framework for discussing these complexities is suggested in
Figure 1. Disparities in underlying social and physical determinants
are embodied and expressed through biological responses and
genetic pathways, which may lead to disparities in risk for obesity
and comorbidities. Differential risk in obesity and comorbidities
may then lead to disparities in survivorship outcomes. All of these
relationships operate in a feedback loop of biological–environmen-
tal interactions. In this review, we evaluate the evidence needed to
answer questions regarding these complexities and make recom-
mendations for future research.
Obesity, Disease-Free Survival,
Nearly 10 years have passed since the publication of the landmark
study by Calle et al., which reported that compared with men and
women of normal weight, for those who were very obese (BMI >
40.0 kg/m2) the relative risk (RR) for death from cancer was 1.52 for
women and 1.62 for men (7). Since then, numerous cohort studies
on this topic have been published, with the majority focusing on
prostate cancer (8–12) and postmenopausal breast cancer (12–14)
and only a few focusing on colorectal cancer (12,15).
Although obesity is an established risk factor for incidence of
several cancers, the impact of obesity on cancer survival is not well
understood. It is unknown whether the greatest risk associated with
obesity occurs before diagnosis (reflecting the role of obesity as a
risk factor for incident disease) or whether weight gain or loss dur-
ing or after treatment has a greater influence on prognosis. Clearly,
each could be relevant. Understanding the difference is important
to developing appropriate interventions to reduce the burden of
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JNCI | Review 1345
A recent large systematic review of the current evidence linking
body adiposity to prognosis in prostate, colorectal, and breast cancer
concluded that most of the 33 studies reviewed supported an asso-
ciation between body adiposity and site-specific mortality or cancer
progression (16). However, most studies included were not designed
to evaluate this association, not all studies controlled for other life-
style factors that may influence survival, and causal inference from
observational research can be limited by measurement error, making
it challenging to disentangle the true independent effect of obesity.
A randomized controlled trial would offer the strongest design to
answer remaining questions, but long-term randomized controlled
trials with sufficient sample size to accrue cancer endpoints are chal-
lenging both with regard to logistics and financial feasibility.
Several smaller systematic reviews were also identified that eval-
uated the association of obesity and survival in breast, endometrial,
and ovarian cancer (17–19). These studies also supported an asso-
ciation of obesity with poorer survival with the caveat that further
studies are needed to confirm the findings, given limitations inher-
ent to observational studies, issues of limited statistical power, and
A recent systematic review and meta-analysis included six
population-based cohorts with data on prediagnosis BMI and
prostate cancer mortality (11). The pooled relative risk for prostate
cancer mortality was 1.15 (95% confidence interval [CI] = 1.06 to
1.25) for each 5 kg/m2 increase in BMI. For an additional six studies
with data from prostate cancer patient cohorts, the pooled relative
risk for mortality was 1.20 (95% CI = 0.99 to 1.46) for each 5 kg/m2
increase in BMI (11). Another study on prostate cancer noted that it
is possible that obese patients develop more aggressive tumors (20).
A Baltimore area cohort study of prostate cancer patients observed
that postdiagnosis weight gain was associated with a twofold
increased risk of prostate cancer recurrence, but specific mortality
estimates were not reported (10). Overall, although the findings
to date are suggestive regarding the association of obesity with
prostate cancer survival, additional data are needed, particularly for
subgroups known to have poor outcomes, including black men.
Evidence to support obesity as a risk factor for incident colo-
rectal cancer is fairly strong and consistent (12,15,21), but data
are relatively sparse with regard to prognosis and survival. Of
1096 incident colorectal cancer case subjects in the Iowa Women’s
Figure 1. Framework for the combined influence of race and obesity
on cancer survivorship. The bottom Venn diagram represents distal
determinants of disparate cancer survival outcomes. Disparities in
these underlying social and physical determinants are embodied and
expressed through biological responses and genetic pathways, which
lead to disparities in risk for obesity and comorbidities. In the top
Venn diagram, differential genes, obesity, and comorbidities then lead
more proximally to disparities in survivorship outcomes. All of these
relationships operate in a feedback loop of biological–social–physical
environment interactions, making it difficult to disentangle which of the
underlying or mediating factors are the greatest contributors to dispari-
ties in survivorship.
Recurrence and Adverse Treatment Effects
Laws, Policies, Norms,
Economics, Health Care,
Kinship and Coworker
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Vol. 105, Issue 18 | September 18, 2013
1354 Review | JNCI
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This work was supported by grants from the National Institutes of Health
(U54-CA155850 at University of Pennsylvania [KHS, LTD]; U01CA116850
at the Fred Hutchinson Cancer Research Center [MLN]; 1U54CA155435
at University of California at San Diego [LC-B]; and U54 CA155496 at
Washington University [BFD]).
Affiliations of authors: Center for Clinical Epidemiology and Biostatistics,
Abramson Cancer Center Perelman School of Medicine, University of
Pennsylvania, Philadelphia, PA (KHS, LTD); Division of Public Health Sciences,
Fred Hutchinson Cancer Research Center, Seattle, WA (MLN); Division of
Cancer Control and Population Sciences, National Cancer Institute, Bethesda,
MD (TA-C, KAZ); Moores Cancer Center, University of California, San Diego,
CA (LC-B); Department of Surgery, Washington University, St. Louis, MO
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