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Like fingerprints, cases of prostate cancer differ
from man to man, depending on many particulars—his age, for instance,
or PSA, or even the ratio of cancer cells that are nourished by
male hormones, compared to those that aren’t. It’s a terribly
individual disease. So why is Bruce Trock, Ph.D., so interested
in looking at the bigger picture?
Because he’s an epidemiologist. Actually, he’s
the first of a first—the new director of the Brady Urological
Institute’s brand new division of Epidemiology, the first of its
kind in any urology department in the country; the division was
launched by a gift from philanthropists Helen and Peter Bing.
And epidemiology, Trock explains, is the connection between basic
science and the clinic. “A scientist like Bill Nelson or John
Isaacs might be looking at something in the lab—a new marker for
detection, or a preventive agent, or a risk factor—or examining
30 specimens of prostate tumor and measuring something. We examine
it in 300, or 500, or 1,000 people, so we can find out whether
it works differently in older men than younger men, in black men
versus white men, in men who have a family history versus those
who don’t. All of these aspects are important in how the disease
actually manifests itself in the population.”
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So many variables, and so many different
groups of men—who make up the word epidemiologists love to use,
“populations.” “That’s part of the challenge,” says Trock. “It’s
like a puzzle, a detective story. How do the pieces fit together?”
Trock, who came to Hopkins from Georgetown
University, “brings unique strengths that enhance our translational
research efforts,” says Urologist-in-Chief Patrick C. Walsh, M.D.
Trock’s distinguished research—in cancer of the breast as well as
the prostate—has made important contributions to the understanding
of diet and breast cancer. Trock also made the first comprehensive
assessment of a particular gene, called the multi-drug resistance
gene, to show that it is commonly expressed in breast cancer, and
is a strong predictor of resistance to chemotherapy. “It’s unusual
to find someone with strong credentials in epidemiology and biostatistics
who can successfully bridge his work with clinical and basic science,”
says Alan Partin, M.D., Ph.D., Bernard Schwartz Distinguished Professor
of Urologic Oncology, who recruited Trock to Hopkins, and who will
be working with him on many projects.
Trock’s research at Hopkins is focused
on four major areas:
Causes.
What sparks prostate cancer? How do environmental or dietary exposures
cross-pollinate with the body’s basic gene makeup? “We’re looking
at oxidative damage, at diet, at what normal processes of the body,
normal function of the prostate, and normal aging of the prostate
make it susceptible to cancer,” says Trock.
He’s also zeroing in on exposure to
cadmium. “Some studies have shown that men in certain occupations,
with higher levels of exposure to cadmium, have a higher risk of
prostate cancer.” Laboratory rats that are given cadmium are known
to develop prostate cancer, and cadmium has been shown to mimic
some effects of male and female hormones. “Cadmium interacts with
the hormone receptors in a way that’s similar to estrogen or testosterone,”
says Trock. “So it’s possible that it can stimulate growth of the
prostate in an abnormal way.” Cadmium also may push beneficial zinc
out of the prostate. Autopsy studies have shown that men who die
from prostate cancer have more cadmium in their prostate than other
men. And of all the body’s organs, guess which one has the highest
concentration of cadmium? The prostate. Apparently, once cadmium
enters the body, it stays put. “It’s very metabolically inert,”
Trock explains. “You can get cadmium in your body, and it will stay
there for 20 years.”
Baltimore is a natural for studying
cadmium exposure—it’s an issue for men who build and repair ships,
welders, men who work in canning factories, men who are exposed
to paints, and a risk of soldering, galvanizing, and electroplating.
“We’re mapping the city for areas that potentially had higher cadmium
exposure. Then we’ll take the highest-exposure zip codes, and whenever
a man comes here to be biopsied for prostate cancer, if he’s from
one of those zip codes, we’ll take a sample of his biopsy. With
the men who turn out to have cancer, we’ll see whether they have
more cadmium in their prostates than the men who didn’t.”
Clinical
biomarkers. Trock is interested in tapping (literally)
a largely unexplored area in prostate cancer research—prostatic
fluid. In the past, it was difficult to obtain prostatic fluid for
examination. However, today it is easily collected from surgical
specimens.
One of the prostate’s main jobs is
to contribute a bit of fluid to the mixture that makes up semen.
“Prior to ejaculation, the sperm are kept in an inactive form,”
explains Trock, “they don’t have much movement. But when they mix
with the prostatic fluid, that seems to activate them and make them
move around a lot, so they are ready to seek out the egg.” There’s
an abundance of reactive oxygen in semen and prostatic fluid, and
“a lot of research in fertility that’s looking at the effects of
oxidative stress on the viability of sperm. So we know that oxidative
stress is being generated in that process. Is any of that affecting
the prostate? Does this over time lead to some sort of irritation
or inflammation? Are certain groups of men more susceptible to this,
perhaps men with lower levels of a protective enzyme, or lower levels
of dietary antioxidants?” Trock also believes that studying the
prostatic fluid can shed light on normal aging of the prostate.
Chemoprevention.
Does eating spaghetti several times a week somehow
help prevent prostate cancer? Does broccoli make your body more
cancer-proof? Trock is ready and able to investigate, taking advantage
of the many compounds being identified and studied in Brady laboratories.
“There’s the potential to do relatively quick studies with these,”
says Trock. One easy, short-term period for testing a chemopreventive
agent is the time between a man’s diagnosis with prostate cancer
and radical prostatectomy. The removed prostate is then compared
to the “before” snapshots of the needle biopsy, to see if anything’s
changed, “if something is altered in a way that suggests there would
be a lower risk if the man didn’t already have the disease,” Trock
explains. “Are we decreasing the growth rate of the cells, decreasing
PSA, enhancing the level of normal cell death? All of these can
be measured with what we call ‘surrogate endpoint biomarkers.’ They
tell us if we’re altering the biology in a beneficial way, and provide
insight into what we really want to know, which is, Does it change
the risk?”
Quality
of life. Ideally, a man’s cancer is diagnosed early,
he’s treated at a “high-volume” center—a place like Hopkins, where
radical prostatectomy is done every day— by an experienced surgeon.
He has minimal side effects, then it’s over. He gets his life back,
and the whole thing, from biopsy to recovery, is just a “blip” on
the radar screen of his life. But for many men, this doesn’t happen.
“How do variations in treatment affect a man’s quality of life?
How do the symptoms that he experiences afterward affect it?” It’s
hard enough comparing surgery patients to surgery patients, harder
still comparing these men to men who have undergone radiation therapy.
“There are many papers that compare results in men who’ve had radiation
to men who’ve had prostatectomy,” says Trock, “but in fact, those
are not comparable. There are many differences that come into play—particularly,
different ways to compute survival rates in one group compared to
another. So how can you get a valid comparison, short of doing a
trial where you randomly assign some men to radiation, and some
to prostatectomy?” Lars Ellison, a Robert Wood Johnson research
scientist, will collaborate with Trock on a study of men who receive
treatment at nationally recognized “centers of excellence” for radiation
or radical prostatectomy.
In the most ambitious project so far,
Trock is one of several scientists planning a super-sized study,
involving possibly 100,000 Baltimore-area men and women. One major
focus would be prostate cancer risk, side effects, progression,
and prognosis. “There are a number of these very large-scale cohort
studies, but none with a heavy urban component. We’re going to be
looking at a population that’s representative of Baltimore—a high
representation of African American men, men in other ethnic groups
who have different levels of prostate cancer risk. This will encompass
Brady, the Kimmel Cancer Center, the School of Hygiene and Public
Health, and it will be going on for 10 to 20 years.”
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