Is the Women’s Health Initiative (WHI) Dietary Modification Associated With a Reduced Risk of Pancreatic Cancer?
JNCI J Natl Cancer Inst (
Is the Women's Health Initiative (WHI) Dietary Modification Associated With a Reduced Risk of Pancreatic Cancer?
Rachael Z. Stolzenberg-Solomon 0 1
Hormuzd A. Katki 0 1
0 Institute, National Institutes of Health , 9609 Medical Center Drive, Room 6E420, Rockville, MD 20850 , USA
1 Affiliations of authors: Metabolic Epidemiology Branch and Biostatics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Rockville MD , USA
Diet may play a role in the prevention of pancreatic cancer (
however, healthy patterns have variably been associated with
pancreatic cancer in case-control and cohort studies (
Dietary exposures are challenging to study in epidemiologic
studies due to measurement error, and large studies are needed
to detect modest magnitudes of risk. Diet is particularly difficult
to examine in epidemiologic studies of pancreatic cancer
because cases often have symptoms of latent disease such as
diabetes, gastrointestinal issues, and weight loss, which can
influence dietary intake. Randomized trials are considered the
“gold standard” of study designs in determining the efficacy of
interventions. The study reported by Jiao et al. (
) in this issue of
the Journal is a worthy effort to evaluate whether a healthy
lowfat dietary pattern affects incident pancreatic cancer.
Jiao et al. (
) report findings from the Women’s Health
Initiative (WHI) Dietary Modification Trial that evaluated the
effects of a low-fat dietary pattern and subsequent risk of
incident pancreatic cancer in postmenopausal women with
extended follow-up for an additional nine years after the
intervention ended. The dietary intervention promoted reducing
total fat intake to 20% of energy and increasing consumption of
vegetables and fruit to at least five servings per day and grains
to at least six servings per day (
). The comparison group was
asked not to make dietary changes (
). Consistent with the
original WHI report (
), no statistically significant association
(hazard ratio [HR] ¼ 0.86, 95% confidence interval [CI] ¼ 0.67 to 1.11)
was observed for the effect of the low-fat dietary intervention
on subsequent incident pancreatic cancer during the core
intervention up to 2005 or during the extended follow-up through
2014 (weighted log-rank P ¼ .23). The authors did, however,
observe a protective association (HR ¼ 0.71, 95% CI ¼ 0.53 to 0.96)
for the low-fat diet intervention among participants who were
overweight or obese (body mass index [BMI] > 25 kg/m2). They
also showed a positive association (HR ¼ 1.62, 95% CI ¼ 0.97 to
2.71) among women who were normal weight (BMI < 25 kg/m2)
at baseline (Pinteraction ¼ .01).
We agree with the authors regarding the limitations of
conducting post hoc analyses of the WHI Dietary Modification Trial
and that caution needs to be taken in interpreting study
findings based on subgroup analyses. A concern about the present
study is that pancreatic cancer is a secondary outcome of the
WHI Dietary Modification Trial. In addition, participants in the
trial had less than optimal adherence to the dietary
modification, and the differences between the intervention and control
groups fell short of the goal for which the study was designed
). The number of pancreatic cancer cases included in the
present study is modest (n ¼ 257). The trial was not powered to
examine pancreatic cancer as an outcome or an interaction of
the trial intervention with other variables. When a study detects
an effect that it is not adequately powered for, the observed
effect may be stronger than the truth. That is, in underpowered
studies, observed statistically significant effects, either
protective or harmful, are often too pronounced. Extreme care is
warranted in the interpretation of the inverse associations in the
subgroup of women who were overweight or obese at baseline
(n ¼ 197), as well as the positive associations observed among
the normal weight women (n ¼ 60). Subgroup associations
found in trials are known to be unreliable, and one might expect
spurious subgroup effects to be identified when none exist
). Further, given the multiple comparisons from the other
stratified analyses and interactions that were tested, the
interaction by baseline body mass index may be due to chance.
Although the results in the subgroup of women who were
overweight or obese are suggestive, they could be misleading.
Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.
In our judgment, the results from this randomized trial do not
clearly support that adhering to a low-fat healthy dietary pattern
reduces the risk of pancreatic cancer. As it is unlikely that large
dietary trials will be conducted with pancreatic cancer as an
outcome, additional studies are needed to demonstrate associations
between healthy dietary patterns and risk of pancreatic cancer.
The authors have no conflicts of interest to declare.
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