From Science News article - melatonin and cancer interaction

January 7, 2006

This is pretty interesting, especially those who work night shifts (or can't

sleep). (http://www.sciencenews.org/articles/20060107/bob9.asp)

Arne

54 - UC 9/77 - PSC 4/00

Alive and (mostly) well in Minnesota

Science News Online

Week of Jan. 7, 2006; Vol. 169, No. 1

Bright Lights, Big Cancer

Melatonin-depleted blood spurs tumor growth

Ben Harder

In late 1987, G. s, 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 s 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.

[iMAGE] 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 s 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 s,

currently at the University of Connecticut Health Center in

Farmington.

" Now, a watershed study has provided the first strong experimental

support, " s 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 E. Blask of the Bassett

Research Institute in stown, 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 . " 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 s. 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 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, " s 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 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, s 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 Jefferson University in Philadelphia,

researchers led by 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 stown, 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.

s 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 , 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 . 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.

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References:

Blask, D.E., G.C. Brainard, et al. 2005. Melatonin-depleted blood

from premenopausal women exposed to light at night stimulates growth

of human breast cancer xenografts in nude rats. Cancer Research

65(Dec. 1):11174-11184. Abstract available at

http://cancerres.aacrjournals.org/cgi/content/abstract/65/23/11174.

Schernhammer, E.S., and S.E. Hankinson. 2005. Urinary melatonin

levels and breast cancer risk. Journal of the National Cancer

Institute 97(July 20):1084-1087. Abstract available at

http://dx.doi.org/10.1093/jnci/dji190.

Schernhammer, E.S., et al. In press. Urinary 6-sulfatoxymelatonin

levels and their correlations with lifestyle factors and steroid

hormone levels. Journal of Pineal Research. Abstract available at

http://dx.doi.org/10.1111/j.1600-079X.2005.00285.x.

Verkasalo, P.K.... R.G. s, et al. 2005. Sleep duration and

breast cancer: A prospective cohort study. Cancer Research 65(Oct.

15):9595-9600. Abstract available at

http://cancerres.aacrjournals.org/cgi/content/abstract/65/20/9595.

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