References & Sources at
http://www.sciencenews.org/articles/20060107/bob9.asp

"Light at night is now clearly a risk factor for breast
cancer," Blask says. "Breast tumors are awake during the day,
and melatonin puts them to sleep at night." Add artificial
light to the night environment, and "cancer cells become
insomniacs," he says. ---

http://www.sciencenews.org/articles/20060107/bob9.asp

Science News, Vol. 169, No. 1, Jan. 7, 2006, p. 8.

Bright Lights, Big Cancer

Melatonin-depleted blood spurs tumor growth

Ben Harder

In late 1987, Richard G. Stevens, then at Pacific Northwest
Laboratories in Richland, Wash., typed up a short letter and
mailed it to Walter Willett at Harvard Medical School in
Boston. The two epidemiologists had met just once, and Stevens
wasn't confident that his 209-word note, or the suggestion that
it contained about a possible contributor to breast cancer,
would inspire any action.

THIS WAY TO CANCER. Just after exposure to bright nighttime
illumination (left), woman produces blood (center) that
contains little melatonin and stimulates the growth of a
human-breast tumor that has been implanted in a rat (right).

Adapted from Blask et al., Cancer Research, with permission

But Willett took the suggestion seriously. He and his
colleagues began a study that only they could do. They run the
Nurses' Health Study, a project unrivaled in scope and duration
that tracks how women's health relates to diet, activity, and
other factors.

Several years later, members of Willett's team reported that
women who frequently work night shifts seem predisposed to
develop breast cancer.

It was just as Stevens had suspected. He had hypothesized that
nighttime illumination, by interrupting the body's mainly
nocturnal production of the hormone melatonin, might increase
the risk of breast cancer. Animal experiments and surveys of
people over the past 2 decades supported that hypothesis
without proving it, says Stevens, currently at the University
of Connecticut Health Center in Farmington.

"Now, a watershed study has provided the first strong
experimental support," Stevens says.

A woman's blood provides better sustenance for breast cancer
just after she's been exposed to bright light than when she's
been in steady darkness, researchers led by David E. Blask of
the Bassett Research Institute in Cooperstown, N.Y., report.

"Light at night is now clearly a risk factor for breast
cancer," Blask says. "Breast tumors are awake during the day,
and melatonin puts them to sleep at night." Add artificial
light to the night environment, and "cancer cells become
insomniacs," he says.

"Sleep per se is not important for melatonin," says Russel J.
Reiter, a neuroendocrinologist at the University of Texas
Health Science Center in San Antonio. "But darkness is."

The new study has far-reaching implications, says Reiter.
First, it could spawn trials that test whether malignancies can
be slowed down by altering a person's light environment or by
using melatonin supplements. Second, he says, similar studies
could show whether exposure to nocturnal light poses a prostate
cancer risk to men, as some researchers suspect, or promotes
other cancers previously linked to light at night (SN: 8/28/04,
p. 141: Available to subscribers at
http://www.sciencenews.org/articles/20040828/note11.asp).

When cancer awakens

Melatonin forms in the pineal gland, located in the brain, and
circulates in the bloodstream. Blood concentrations of the
hormone rise after dark from low daytime values and usually
peak in the middle of the night.

Because the pineal gland responds to signals transmitted by the
optic nerves, bombarding a person's eyes with bright light
during the night can erase the usual nocturnal surge and lower
the overall melatonin production for the day. That observation
concerned researchers, in part because melatonin has slowed
breast cancer growth in lab experiments.

Then, there's the disturbing circumstantial evidence.

"Breast cancer is epidemic in the world. It's increasing
everywhere," says Stevens. It's most prevalent in
industrialized countries, where electric lights are widely
used, he says. "It's increasing very rapidly in places that are
industrializing," he adds.

Furthermore, compared with other workingwomen, female
night-shift workers have about a 50 percent greater risk of
developing breast cancer, says William Hrushesky of Dorn
Veterans Affairs Medical Center in Columbia, S.C.

Blind women, by contrast, have unusually low rates of breast
cancer and high average melatonin concentrations, he says.

"Almost nobody who does shift work adapts to it," Stevens says.
On their days off, most shift workers concentrate their
activities during daylight, which upsets their circadian
rhythms as much as commuting across several time zones would,
he says.

That presumably explains why the original Harvard study of
nurses, which was led by Willett's colleague Eva S.
Schernhammer, found that shift workers had an elevated risk of
breast cancer (SN: 11/17/01, p. 317: Available to subscribers
at http://www.sciencenews.org/articles/20011117/note16.asp).

More recently, Schernhammer and her Harvard colleague Susan E.
Hankinson found that women who happen to have above-average
melatonin concentrations are relatively unlikely to develop
breast cancer.

The Harvard researchers estimated nurses' peak nightly
melatonin concentrations by measuring the hormone in the first
urine void of a day. "Those with higher levels seem to have
lower breast cancer risk," Schernhammer says. She and Hankinson
reported the data in the July 20, 2005 Journal of the National
Cancer Institute.

An earlier study didn't find the same statistical relationship,
but it had involved melatonin measurements in urine samples
taken later in the day. Such samples are less likely to
correlate with nocturnal hormone concentrations, says
Schernhammer.

She notes that light is not the only relevant factor. Age and
obesity both reduce a person's melatonin production, and heavy
smoking may do the same, she says. She and other researchers
will report the first data that support the smoking-melatonin
relationship in an upcoming Journal of Pineal Research.

Breast cancer is less common in women who sleep more than 9
hours per night than in women who sleep less, Stevens and six
colleagues in Finland report in the Oct. 15, 2005 Cancer
Research. They compared cancer incidence in 12,222 Finnish
women whose average nightly sleep duration had been recorded in
1975 and 1981. By 1996, 242 of the women had developed breast
tumors.

Women who consistently slept 9 or more hours per night had less
than one-third the risk of developing a breast tumor than women
who slept 7 or 8 hours per night.

Now, Blask and his collaborators at several institutions have
pushed beyond studies finding correlations among cancer, light,
and melatonin. At Thomas Jefferson University in Philadelphia,
researchers led by George C. Brainard asked each of a dozen
healthy female medical students to give three blood samples,
one during the day and two at night.

The first nighttime blood draw occurred at 2 a.m., after each
woman had been in complete darkness for 2 hours. Then the
volunteers stared at a brightly lit, white wall for 90 minutes,
and the second nighttime draw took place at 3:30 a.m.

As expected, blood from the 2 a.m. samples contained the
highest concentrations of melatonin, and daytime blood
contained the lowest. Brainard then sent the samples to Blask
for an unusual test of their effect on human-cancer cells.

In Cooperstown, Blask and his colleagues had implanted human
breast tumor into rats in such a way that a single artery fed a
tumor and a single vein received all blood leaving the
cancerous tissue. The team then put plastic tubes into the two
vessels, creating external conduits to and from the tumor. The
researchers also shut the cancerous tissue off from the rest of
the rat's circulatory system.

Next, they pumped each blood sample from the Philadelphia
medical students into a separate rat's arterial tube and
collected the liquid as it came out of the cancerous human
tissue. By comparing what blood components went in and what
came out, the researchers assessed the tumors' responses to the
concentrations of melatonin in the samples. For example, they
measured the tumors' uptake of H3-thymidine, an ingredient of
DNA that reflects cell division and replication in a tumor.

The results indicated that the tumor cells divided most rapidly
when supplied by blood taken from women either in daylight or
at night after exposure to the bright artificial light. Those
blood samples had low melatonin concentrations. Spiking the
samples with synthetic melatonin removed their capacity to
promote cancer.

Moreover, melatonin-rich blood from women who had been in
darkness spurred cell division only when the researchers added
a chemical that blocks melatonin's biological activity.

In further experiments, Blask's team determined that melatonin
blocks cancer cells' metabolism of linoleic acid, a
polyunsaturated fat that's abundant in food. The same team had
previously shown that 13-hydroxyoctadecadienoic acid, the
product of linoleic acid metabolism, spurs cancer cells to
divide.

The team reports its results in the Dec. 1, 2005 Cancer
Research.

The unusual test in the rats shows "close to conclusively" that
light-induced suppression of melatonin promotes breast-tumor
growth, says Schernhammer.

Stevens adds that Blask's new technique of testing people's
blood on human tumors in animals is a powerful tool for
evaluating the effect of all sorts of actions. Eating a
particular food or inhaling a pollutant, for example, could
alter the blood concentrations of substances that promote or
fight cancer.

Managing melatonin

In the United States, synthetic melatonin is sold over the
counter as a dietary supplement. Blask and other researchers
want to see tests to assess whether the hormone in this form
can ward off breast cancer in women. But they warn that it
would be premature for people to take the hormone for that
purpose.

"I personally would be pretty cautious about taking
over-the-counter melatonin supplements," says Scott Davis, an
epidemiologist at the University of Washington in Seattle.
"Melatonin supplements are not regulated" the way drugs are, he
notes. "There may be all kinds of impurities and contaminants."

Although synthetic melatonin hasn't been shown to be dangerous,
it could have adverse effects on the production of reproductive
hormones, cautions Schernhammer.

Hrushesky is currently testing the possible benefits of
melatonin supplements in men who have undergone surgery for
prostate cancer. For now, though, he encourages people to opt
for commonsense measures to ensure they get nightly melatonin
spikes. Those precautions include going to sleep in the dark at
a consistent time each night, exercising regularly, and
avoiding evening use of melatonin-suppressing substances,
including alcohol and medications such as beta-blockers.

People's behavior after bedtime also counts. "They should avoid
even brief intervals of [bright] light at night," says Reiter.
"A nightlight is generally safe," he adds, because dim light
has relatively little effect on melatonin.

Schernhammer offers similar advice: "If [getting up] to go to
the bathroom, avoid turning on the light, or keep it dim."

But other scientists say that it's unclear how much a quick
trip to an illuminated bathroom affects melatonin in the blood.
"It's probably inconsequential," says Mark Rea, director of the
Lighting Research Center at Rensselaer Polytechnic Institute in
Troy, N.Y.

Reiter offers some other strategies for maintaining melatonin
production. Blue or white light suppresses melatonin more
effectively than red or yellow does (SN: 4/16/05, p. 253:
Available to subscribers at
http://www.sciencenews.org/articles/20050416/note12.asp), so
lights could be designed to filter out the offending
wavelengths, Reiter says. Or people could strategically don
tinted, wraparound glasses to achieve the same result, he says.

Night-shift workers face fundamental challenges, Blask says.
"Melatonin works, to a large degree, by inhibiting the cancer
cells from taking up linoleic acid," he says. Cravings for
fatty foods frequently assail workers in the middle of the
night. As a result, many shift workers consume large amounts of
linoleic acid just when their melatonin production is
suppressed and unable to protect them from the polyunsaturated
fat, he says.

In addition to its direct effect on breast cancer, melatonin
may indirectly combat tumor growth, says Davis. Melatonin
suppression encourages the ovaries to produce estrogen and
other female sex hormones, which support the growth of
cancerous or potentially cancerous cells in a woman's breasts.

If future studies demonstrate such indirect hormonal effects,
they'll reveal yet one more way by which nighttime light
exposure feeds cancer.

References & Sources at
http://www.sciencenews.org/articles/20060107/bob9.asp