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Studying the Connection Between Exercise
and Cancer Risk Reduction
By Leslie Harris O’Hanlon
W
hen Leslie Bernstein, Ph.D.,
submitted a paper that found
when younger women exer‑
cised for 4 hours per week they lowered
their breast cancer risk by 50%, the editor
of the journal refused to publish it because
he didn’t believe the findings. So Bernstein
promptly resubmitted the findings to
another journal, and the study was pub‑
lished in 1994. Since then, dozens of studies
have associated exercise with reduced risk
of breast cancer and many other cancers.
“There are no guarantees because all can‑
cers have multiple causes,” said Bernstein,
professor and director of cancer etiology at
the City of Hope Cancer Center in Duarte,
Calif. “But I can say, looking at large groups
of people, those who exercise tend to have a
lower risk of devel‑
oping some cancers
than those who
don’t.”
Nearly 20 years
after Bernstein pub‑
lished her paper,
researchers are try‑
Christine Friedenreich, Ph.D. ing to better under‑
stand why exercise curbs cancer risk. The
association is strongest in breast and colon
cancer, and e­ vidence is mounting that exer‑
cise is associated with lower risk of endome‑
trial, ovarian, prostate, and pancreatic cancer.
Some studies suggest that exercise helps by
lowering obesity, inflammation, and hor‑
mone levels and improving insulin resist‑
ance and immune system function—factors
involved in cancer formation. Whatever the
reasons, studying the effects of exercise on
cancer risk is important because it may be
one of the few things people can do to reduce
their risk of cancer.
“There are so many risk factors that are
not modifiable, such as genetics or exposure
to external agents that you can’t control,”
said Christine Friedenreich, Ph.D., a can‑
cer epidemiologist with the Department
jnci.oxfordjournals.org
of Population Health Research of Alberta
(Canada) Health Services and an adjunct
professor at the University of Calgary.
“People can control how much they exer‑
cise, and that is what makes this such an
exciting field. It has a lot of potential from a
public-health perspective.”
those who both dieted and exercised. Women
who dieted and exercised also saw the biggest
increases in their SHBG levels. The idea is
that the lower the hormone levels, the lower
the risk of developing breast cancer, said lead
author Anne McTiernan, M.D., Ph.D., a
member of the cancer prevention program
at the Fred Hutchinson Cancer Research
Center in Seattle.
“One can routinely check cholesterol,
Recent Research
Most of the work looking at exercise and hemoglobin A1c, and insulin levels after
cancer prevention has been observational, making lifestyle changes,” she said. “We
meaning that people in such studies fill out don’t have that in cancer yet. Estrogens are
questionnaires or are interviewed about not measured as part of routine practice.”
their physical activity and are followed up
Friedenreich also published studies look‑
for several years to see whether they develop ing at hormone levels in postmenopausal
cancer. Now, some researchers are conduct‑ women who participated in moderate to vig‑
ing randomized controlled exercise trials to orous exercise. In one study, appearing in the
see how physical activity affects cancer bio‑ online October 2011 issue of Cancer Prevention
markers. The results of one trial, published Research, researchers reported that women
last May in the Journal of Clinical Oncology, who exercised saw their levels of C-reactive
found that women who exercised and lost protein, a marker of inflammation linked to
weight lowered their levels of certain sex hor‑ cancer risk, drop. Another study, published in
mones known to spur breast cancer growth. the March 2010 Journal of Clinical Oncology,
The study included 439 overweight to obese found that women who exercised more had
sedentary women, aged 50–75 years, lower blood levels of estradiol and free estra‑
randomly assigned to one of four groups: diol, hormones thought to play a role in breast
exercise only (mainly brisk walking), diet cancer cell growth. Data from both studies
only, exercise plus diet, and no intervention. came from the Alberta Physical Activity and
The study measured how diet- and exercise- Breast Cancer Prevention (ALPHA) trial, related weight loss
an ­exercise inter‑
affected blood levels
vention
study that
“There are so many risk factors
of three forms of
includes 320 post‑­
­
that are not modifiable, such as menopausal women
estrogen; andros‑
tenedione, a ster‑
genetics or exposure to external aged 50–75 years
oid ­
necessary for
and is examining
the production of
the effect of aerobic
agents that you can’t control.”
sex hormones; and
exercise on several
SHBG (sex hormone–binding globulin), risk factors for breast cancer. Friedenreich is
a protein that binds to sex hormones and conducting trials to home in on the levels of
makes them less biologically active. High exercise that might show the greatest reduc‑
levels of SHBG are associated with reduced tion in sex hormones. In one trial, women
breast cancer risk. The researchers found either exercise for 150 minutes per week (five
reductions in hormone levels among women times per week for 30 minutes per day) or for
who received the dietary weight loss inter‑ 300 minutes per week (five times per week for
vention, with the greatest reductions among 60 minutes).
JNCI | News 753
NEWS
“I have a feeling more may be better, but
we really don’t know yet,” she said. “Doing
some activity may be better than nothing,
but it may not be enough to go and walk for
10 minutes. It may need to be longer, more
sustained activity.”
Exercise trials have also clarified how
physical activity can lower colon cancer
risk. A study in the September 2006 Cancer
Epidemiology, Biomarkers, and Prevention
found that men who did at least 1 hour of
aerobic activity 6 days per week for a year
saw a substantial decrease in the amount of
cellular proliferation in the colonic crypts—
tiny tubelike indentations in the lining of
the colon that help regulate absorption of
water and nutrients. Although a certain
amount of cellular proliferation in the bot‑
tom part of the crypt is normal, too much
can lead to polyps. However, the same
effect did not occur in women, according to
McTiernan, lead investigator for the study.
“For colon cancer, sex hormones are
protective. It could have been that because
the women exercised a lot, that lowered
their estrogen levels, which means they lost
some of their protection from colon can‑
cer,” she said.
Recent observational work has also high‑
lighted the connection between cancer and
exercise. A meta-analysis of 20 studies pub‑
lished in the March 2011 British Journal of
Cancer revealed that regular physical exer‑
cise was associated with a 16% decrease in
the risk of developing colon polyps and with
a 30% decrease in the risk of developing
polyps that were large or advanced and thus
more likely to become cancerous. Several
factors could account for these findings,
wrote the researchers, including enhanced
immune function, decreased inflammation,
reduced insulin levels and insulin resist‑
ance, and higher vitamin D levels, all of
which influence formation of colon polyps.
Bernstein cowrote a paper published last
October in Cancer Epidemiology that sug‑
gested normal and underweight women, as
measured by body mass index, who exer‑
cised at least 5.5 hours weekly had a slight
reduction in their risk of developing papil‑
lary thyroid cancer. “Although the results
were suggestive, they require confirmation
in future studies,” she said. She hopes that
other researchers can build on this work.
Next Steps
Many questions need to be answered to
better understand the role of exercise in
cancer prevention. For example, research‑
ers are trying to determine how much exer‑
cise people need to see the most benefit.
General guidelines suggest 150 minutes per
week (30 minutes, five times per week) of
moderate activity. But the American Cancer
Society believes that this number should be
increased to 225 minutes per week (45 min‑
utes per day, 5 days per week).
“What we are seeing for cancer preven‑
tion is that it may require a higher level of
activity to get a benefit, but there is not a lot
of precision or clarity around the recommen‑
dation,” said Alpa Patel, Ph.D., an epidemi‑
ologist with the American Cancer Society.
Also, studies define and measure physi‑
cal activity differently. One study may look
at number of overall minutes, whereas oth‑
ers may classify exercise as moderate or
vigorous. Adding to this messiness in meas‑
urement is that the population groups in
studies are different. All these factors make
generalizing study results difficult.
Moreover, different kinds of exercise
may need to be examined. For instance,
weight training reduces insulin resistance
in diabetics. Insulin resistance, in which
the body produces insulin but does not
use it effectively, has been linked to the
development of some cancers, including
pancreatic cancer. Could weight training
lower cancer risk by improving the body’s
use of insulin?
And some researchers say that to draw
firm conclusions about exercise and cancer
risk reduction, many people would need
to be put into randomized groups that
exercised and groups that didn’t and then
followed up for several years to see who
actually developed cancer.
“There just isn’t enough money to
do those kinds of studies very often,”
McTiernan said.
Still, most experts agree that exercise
at any amount is good for overall health,
including lowering risk for cancer. A study
published last November in PLoS Medicine
found that people older than 40 years who
exercised at an intensity level equivalent
of brisk walking for 75 minutes per week
gained 1.8 years of life expectancy. That
gain was greater at higher levels of exercise
and if people were not overweight or obese.
© Oxford University Press 2013. DOI:10.1093/jnci/djt136
Good and Bad News about Latest Outcomes
for Smoking
By Mike Fillon
I
n 1964, U.S. Surgeon General Luther
Terry released Smoking and Health:
Report of the Advisory Committee to the
Surgeon General of the United States. Before
this, health suspicions about smoking
754 News | JNCI
existed, but not much more than common
parental homilies to adolescents that smok‑
ing cigarettes would “stunt their growth.”
The report presented the first clear
evidence that cigarette smoking could
be linked to lung cancer, bronchitis, and
other chronic and life-threatening dis‑
eases. Many people got the message, and
U.S. smoking rates have fallen, from 42%
of adults in 1965 to 19% in 2010. Even
Vol. 105, Issue 11 | June 5, 2013