Cancer

Contact: Aaron Lohr
alohr@endo-society.org
240-482-1380
The Endocrine Society

Hormone thought to slow aging associated with increased risk of cancer death

Chevy Chase, MD— According to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM), older men with high levels of the hormone IGF-I (insulin-like growth factor 1) are at increased risk of cancer death, independent of age, lifestyle and cancer history.

IGF-I is a protein hormone similar in structure to insulin and is regulated in the body by growth hormone (GH). Levels of GH and IGF-I decline progressively with age in both men and women and this drop is thought to be related to deteriorating health conditions found with advanced age. In an attempt to combat aging some people use GH as its actions elevate IGF-1.This study however showed that older men who had higher levels of IGF-I were more likely to die from a cancer-related cause in the following 18 years than men with lower levels.

"This is the first population-based study to show an association of higher IGF-I levels with increased risk of a cancer-related death in older men," said Gail Laughlin, PhD, of the University of California San Diego, and corresponding author of the study. "Although the design of this study does not explicitly show that the higher IGF-I levels caused the cancer death, it does encourage more study as well as a reexamination of the use of IGF-I enhancing therapies as an anti-aging strategy."

In this study researchers used data on 633 men aged 50 and older from the Rancho Bernardo Study, a population-based study of healthy aging. Study participants took part in a research clinic examination between the years of 1988 and 1991 where their blood was obtained and IGF-1 was measured. All participants had their vital status followed through July 2006. Researchers found that men in this study who had IGF-I levels above 100 ng/ml had almost twice the risk of cancer death in the following 18 years than men with lower levels.

"In this study, the increased risk of cancer death for older men with high levels of IGF-I was not explained by differences in age, body size, lifestyle or cancer history," said Jacqueline Major, PhD, lead author on the study, now at the National Cancer Institute. "If these results are confirmed in other populations, these findings suggest that serum IGF-I may have potential importance as a biomarker for prognostic testing."

###

Other researchers working on the study include: the Principal Investigator and founder of the Rancho Bernardo Study, Elizabeth Barrett-Connor; and Donna Kritz-Silverstein and Deborah Wingard of the University of California, San Diego.

The article, "Insulin-like Growth Factor-I (IGF-I) and Cancer Mortality in Older Men," will appear in the March 2010 issue of JCEM.

Founded in 1916, The Endocrine Society is the world's oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org.

SCIENTISTS FIND A SOUP OF SUSPECTS WHILE PROBING MILK’S LINK TO CANCER

Home / News / March 28th, 2009; Vol.175 #7 / News item

Latest studies focus on estrogens, androgens and IGF-1

By Janet Raloff

March 28th, 2009; Vol.175 #7 (p. 5)

Got milk? Adults who answer yes may face a slightly heightened risk of cancer.

Some emerging data may help scientists figure out why.

For more than a century, people thought that any beverage safe enough to

serve to a weaning child couldn’t hurt an adult. But test-tube studies and studies

in adults over the past decade have linked cow’s milk with an excess cancer risk

in the prostate, and to a lesser extent in the breast and ovaries, notes oncologist

Michael Pollak of McGill University in Montreal. Although scientists seeking to

explain the link have fingered some suspects—such as milk’s natural stew of

hormones, growth factors and other biologically active chemicals—there’s no

“smoking gun,” he says.

But a new study by researchers at the National Cancer Institute at Frederick, in

Maryland, offers some ammunition.

Timothy Veenstra and his colleagues assayed grocery-store milk for 15

estrogens: estrone, estradiol and 13 metabolic derivatives of these female sex

hormones.

Typically, hormones are produced in the body for use in the body. They act as

orchestra conductors, telling genes when to turn on and off. But externally

derived hormones add noise.

Estrogens can fuel the growth of many tumors, even in the prostate--and

estrogen can do this at amazingly tiny concentrations. Identifying how estrogens’

prevalence varies by milk type, and in what chemical form the hormones occur,

required a new assay, which the NCI scientists describe in an upcoming issue of

the Journal of Chromatography B.

Using that technique, they showed that the mélange of estrogens varies widely

between milks. Whole milk contained the smallest quantity of estrogens, and

amounts ascended from 2% to skim and buttermilk. In all of these milks, the

majority of estrogens had undergone a minor chemical modification, rendering

them less directly bioavailable and less hormonally active.

However, these modified, or conjugated, estrogens are not inert, and they can

be converted back to their more potent parent compounds. What’s more, the

NCI scientists note, studies by others have shown that relative to free,

bioavailable estrogens, conjugated ones take longer to get from the gut into the

blood.

Veenstra’s team concludes that compared with free estrogens, milk’s conjugated

ones “are likely to have longer half-lives.”

Overall, skim milk had the smallest quantity of free estrogens. However, the

conjugated type that dominated skim milk’s profile, 2-hydroxyestrone, is known

to be one of the most reactive and potentially risky of the metabolites, notes Xia

Xu, a toxicologist on the NCI team. That metabolite’s concentration in fat-free

milk was second only to buttermilk’s.

Dermatologist F. William Danby, who teaches at Dartmouth Medical School,

also worries about other sex hormones in milk—the “male” androgens.

While estrogens may fuel tumor growth in reproductive tissues, certain

androgens—ones that Danby refers to as 5alpha-reduced androgens—“have

the capacity for increasing the number of estrogen receptors.” In the

January/February Dermato-Endocrinology, Danby notes that milk contains at

least one receptor-proliferating androgen: 5alpha-pregnanedione.

Extra receptors, he explains, permit more estrogen—including any from milk—to

unlock the cellular machinery that can turn tumor growth on. In other hormone

systems, when excess hormone shows up, the body often cuts back on its

production. Because the body has had relatively little evolutionary time to adapt

to dietary sources of the 5alpha-reduced androgens, Danby says, no such

feedback system has evolved.

“And this is probably the most important thing,” he says. Milk-derived hormones

“are being poured into a system that didn’t anticipate them”—at least in

adulthood.

One of the most provocative aspects of the milk story is its impact on insulinlike

growth factor 1. Many studies have linked elevated concentrations of IGF-1 with

cancer risk. Not only is milk a rich source of the substance, but people who drink

milk also end up with more IGF-1 in their blood.

As with so much in science, however, the IGF-and-milk story is anything but

simple, notes David Kleinberg, an endocrinologist at New York University School

of Medicine.

Ordinarily, IGF-1 production is turned on when human growth hormone,

produced in the pituitary gland, hits certain tissues. IGF-1 becomes the growth

hormone’s agent to locally trigger cell growth.

“We showed that IGF-1 can completely take the place of growth hormone” in

breast tissue, Kleinberg says. In other words, IGF-1 can trigger cell growth

without an outside cue.

Although estrogen is linked to breast development, it’s impotent in the absence

of IGF-1. Estrogen can amplify the cell-proliferating effects seen with IGF-1, his

team has shown — both in the breast and prostate.

In the February Endocrine Reviews, Kleinberg and his colleagues note that

when an excess of IGF-1 or estrogen occurs in the presence of the other, breast

hyperplasia occurs—essentially cell division on overdrive.

“And when you get hyperplasia, it can put one at risk for breast cancer. Very

slightly at risk,” he says, “like maybe less than a doubling of risk.”

But the real kicker: “There’s a lot of interpersonal variability in our natural

production of IGF-1,” Pollak points out. “And even though we are sure that

drinking more milk will increase your IGF-1 level, milk’s contribution will still only

account for a trivial part of the variation between people.”

Which means genetics trumps milk intake. So people who naturally rank in the

Science News / Scientists Find A Soup Of Suspects While Probing Milk’s Link To Cancer Page 3 of 4

http://www.sciencenews.org/view/generic/id/41720/title/Scientists_find_a_soup_of_suspec... 3/14/2009

top quarter in terms of IGF-1 production and drink no milk, Pollak explains, “will

still have a higher IGF-1 level than someone in the low quartile who drinks a

quart a day.”

Against this ambiguous backdrop, what’s a milk drinker to do? Because the

body of knowledge about this beverage’s human bioactivity is still in its infancy,

people may just have to employ the precautionary principle, Pollak says.

“In the absence of definitive [safety] data—or the presence of an adverse effect

which may be small—you have to decide: Is there anything good about milk?”

And other than developing children and malnourished adults, people probably

don’t need milk, he says. “I would never say anything stronger than that.”

Hormone link to cancer
from The Courier Mail
Bernadette Condren

September 22, 2007 12:00am

HUMAN growth hormone could be responsible for several types of cancer, including breast cancer, a University of Queensland researcher has found.

Mike Waters, from UQ's Institute for Molecular Bioscience, said the hormone was needed for normal human growth and it worked by using a messenger protein called IGF1 (insulin-like growth factor).

"There's quite a bit of work that implicates IGF1 in promoting cancers so this is an important way that growth hormone could be promoting cancers," Professor Waters said.

Growth hormone is produced by the pituitary gland and stimulates even growth in the body after birth.

It also plays a significant role in metabolism, minimising the amount of fat in the body and stimulating glucose production.

Professor Waters said studies on people whose pituitary glands failed to produce growth hormone showed they remained cancer free.

"In the absence of growth hormone the cancer rate is markedly lower and there's a worldwide survey that's just been done of 220-odd people that didn't find a single malignancy in people who had deficient growth hormone action," he said. "That also correlates with animal studies in rats and mice where without growth hormone you treat them with cancer-causing chemicals and they don't get tumours."

The research could have major implications for the global pharmaceutical industry where the sale of human growth hormone is worth more than $2 billion a year. Human growth hormone is often used by bodybuilders.

Professor Waters said "knocking down" the hormone or blocking its action could inhibit cancer and stop tumour growth.

So far his research has only been able to partially disable the hormone.

"We need to get the knock down more effective – if we can really knock it down we should be able to stop a hell of a lot of cancers," Professor Waters said.

In a second-pronged attack on cancer, the professor has found that the target for growth hormone, its receptor, is within the cell nucleus.

"So we've sent the receptor to the cell's nucleus using a special means and that's caused the cell to become cancerous," he said of the research that has been published by the National Academy of Sciences in the US.

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

Science Daily — April 7, 2007 WINSTON-SALEM, N.C. Deficiencies of growth hormone and similar compounds may reduce cancer and kidney disease late in life, but also may lead to cartilage degeneration and impaired memory and learning ability, according to research at Wake Forest University Baptist Medical Center and four other institutions.The researchers used a rat model to explore the effects of growth hormone and another compound, IGF-1 (insulin-like growth factor 1) on adult rats and found paradoxical effects, according to William E. Sonntag, Ph.D., professor of physiology and pharmacology at Wake Forest University Baptist Medical Center and the lead investigator.

"Things that happen when you are an adolescent may have an impact on how long you live and what you die of," he said.

"The presence of growth hormone and IGF-1 is necessary for maintenance of cognitive function and prevention of cartilage degeneration," Sonntag and his colleagues reported in an article in Endocrinology, published on-line today. But the hormones also increase cancer and other diseases that limit lifespan.

The researchers developed a strain of dwarf rats that were naturally deficient in both growth hormone and in IGF-1. To mimic the rise in growth hormone and IGF-1 during adolescence in normal rats, some of these deficient rats were given growth hormone while they were between 4 and 14 weeks of age rat adolescence. Then hormone treatment was stopped and the animals had lower growth hormone and IGF-1 levels the rest of their lives.

That had an effect on cancer: 88 percent of "normal" male rats have tumors at death. The male rats that had a lifelong deficiency of growth hormone had substantially fewer tumors 63 percent and the percent of tumors that were fatal was reduced from 57 percent to 31 percent.

The same pattern occurred for kidney disease, which was found in 74 percent of the normal male animals at the time of their deaths. None of the growth-hormone deficient animals developed kidney disease.

They found that animals with a deficiency in growth hormone initiated after adolescence had up to a 14.6 percent increase in lifespan. All animals in the study lived until they died of natural causes.

The researchers used several tests to measure memory and learning. They found that growth-hormone-deficient rats had impaired learning ability compared to normal animals of the same age. A similar pattern occurred in memory tests.

"The presence of growth hormone and IGF-1 are required for optimal performance on tests of learning and memory throughout life," they said. "Growth hormone/IGF-1 replacement in older animals reverses the age-related decline in cognitive function."

The group also found that "cartilage degeneration that normally accompanies aging is accelerated by the absence of growth hormone."

The researchers concluded that cancer risk as well as other age-related pathologies could be substantially decreased in these animals by inducing a modest deficiency of growth hormone and IGF-1 early in life. However, there is a tradeoff and deficiency of growth hormone and IGF-1 may impair learning and memory and accelerate some degenerative diseases.

Note: This story has been adapted from a news release issued by Wake Forest University Baptist Medical Center.

The Increased Risk For Cancer and Agressive Metasteses (spreading of cancer) With GH Administration to Normal Adults

Cancer and IGF-1
By Dr. Joseph Mercola
www.mercola.com

In a recent editorial in the British Medical Journal [October 7, 2000;321:847-848], several experts from the University of Bristol in England write about the substantial and still growing body of evidence implicating insulin-like growth factor-I (IGF-1) in cancer.

They note that the role of IGF-1 in promoting cancer has been investigated for many years, but recently the quality and quantity of evidence has increased

They note that several prospective studies have used stored blood collected up to 14 years before the onset of cancer have shown associations between IGF-1 and prostate cancer, premenopausal breast cancer, and colon cancer.

According to the editorial, "The risk of cancer is higher among people with raised concentrations of insulin-like growth factor-I".

In addition, "it is lower among those with high concentrations of insulin-like growth factor binding protein-3 (the main binding protein)."

Research suggests that the observed relation between cancer and IGF-1 is not due to the release of the growth factor by the cancer itself.

"The effects are sizeable and stronger than the effects seen in relation to most previously reported risk factors" they state.

In addition to the increasing direct epidemiological evidence, there is a significant amount of circumstantial evidence.

Acromegaly, in which high concentrations of growth hormone stimulate production of high concentrations of IGF-1, has been associated with an increased risk of colorectal cancer and breast cancer in some studies and less consistently with prostate, thyroid, and hematological malignancies.
In many studies anthropometric markers of the activity of insulin-like growth factor-I, such as height and leg length, are associated with cancer incidence, particularly with the cancers for which risk increases with rising concentrations of insulin-like growth factor-I.
In animals, calorie restriction reduces the risk of cancer primarily by reducing the circulating concentrations of insulin-like growth factor-I" the editorial notes.

Some of the potential mechanisms of the way in which IGF-1 increases cancer risk are as follows:

IGF-1 could be a surrogate for the activity of sex steroid hormones, which in turn influence the risk of cancer.
IGF-1 may increase cell turnover and the susceptibility of cells to malignant transformation both directly and by modulating the effects of sex steroids.
IGF-1 might increase the risk of cancer by preventing the programmed death of cells that have been transformed, thus interrupting an important process, which retards the development of cancer.

"Given the increasing evidence of the risk of cancer, caution should be exercised in the exogenous use of either insulin-like growth factor-I or substances that increase concentrations of it," they state.

British Medical Journal October 7, 2000;321:847-848

DR. MERCOLA'S COMMENT: Many may not realize that when you drink milk you are consuming IGF-1, along with many other growth factors. Milk from cows treated with synthetic growth hormones such as rBGH have especially high levels of IGF-1. This is one of the many reasons why I advise avoiding milk. You can click on the links below for the others.

It is also interesting to note that the growth hormone that is so strongly promoted by many anti-aging clinicians may in fact have adverse effects by raising insulin-like growth factor-I. It is probably best for most to avoid the use of growth hormone and rely on more proven and less risky interventions, like a good diet which reduces insulin levels and also weight training which can increase growth hormone.

©Copyright 2003 Dr. Joseph Mercola. All Rights Reserved. This content may be copied in full, with copyright, contact, creation and information intact, without specific permission, when used only in a not-for-profit format. If any other use is desired, permission in writing from Dr. Mercola is required.

Fair Use Notice: This document may contain copyrighted material whose use has not been specifically authorized by the copyright owners. We believe that this not-for-profit, educational use on the Web constitutes a fair use of the copyrighted material (as provided for in section 107 of the US Copyright Law). If you wish to use this copyrighted material for purposes of your own that go beyond fair use, you must obtain permission from the copyright owner.

Cancer took life of noted user of growth hormone

Sabin Russell, Chronicle Medical Writer

Thursday, June 8, 2006

When 56-year-old Hanneke Hops was profiled in The Chronicle in November 2003, the Hayward woman said her daily injections of human growth hormone were making her feel stronger, happier and healthier.An athlete all her life, she looked forward to running marathons, riding her horses and flying private planes -- with a boost from the genetically engineered drug that had never been approved as an anti-aging medicine. "I don't mind dying,'' she said in an interview. "But I mind growing old and suffering... If we are not healthy, how can we accomplish our goals in life?"

Three months after the story appeared, she was dead from cancer. A test that January found her liver riddled with tumors. It was inoperable. No link to her use of human growth hormone and her sudden and totally unexpected decline in health has been established, but Hops' friends and family remain suspicious that her death was somehow related to those injections.

"I believe it accelerated a cancer she must have had already,'' said her son, Erick Schenkhuizen, a San Diego financial adviser. "If she hadn't taken the hormones, she could still be alive today.'' In the three years since Hops died, America's fascination with antiaging medicine has only increased. Business has been booming at the Cenegenics Medical Institute, the Las Vegas clinic that prescribed human growth hormone to Hops.

"There's a huge demand for this,'' said Dr. Alan Mintz, the 68-year-old entrepreneurial radiologist who founded Cenegenics nine years ago. "We have 12,000 patients. We're opening up in Charleston, and Boca Raton."
Mintz said Wednesday that he did not know Hops had died. "I'm a radiologist. I never get involved in the clinical care of our patients,'' said Mintz. He said Cenegenics would not have treated Hops with hormones if she had cancer. A cancer screen is a routine part of the medical workup given to patients before they start on hormone therapy. Hops began her treatments in August 2003.Nevertheless, Mintz said that there is "not a single article" that directly links human growth hormone to cancer. "Speculation is one thing.Facts are another,'' he said.

Hops began complaining of stomach pains in October 2003, but dismissed it as indigestion. By December, her health had deteriorated markedly. Still, she kept taking the costly human growth hormone shots -- $23 a day -- through the New Year. On Jan. 2, 2004, an ultrasound detected abdominal masses, and soon after her terminal cancer was diagnosed. She died at home just seven weeks later, on Feb. 21.

Schenkhuizen said he likely will never know for certain if the hormones cost his mom her life. Her sons and family friends had disapproved of her experiment in anti-aging medicine. "It was a touchy topic with her,'' Schenkhuizen said. Hops said just months before her cancer was diagnosed that she believed the risk was minimal. Her mother had recently died of

Alzheimer's disease, and she said she was determined to live her life to the fullest -- she didn't want to see her own life end in the same prolonged manner as her mother's.But by the time Hops died, her son said, she had "many questions and

concerns" about the effect the drug might have had on her.

In an article published in the October issue of the Journal of the American Medical Association, University of Chicago epidemiologist Jay Olshansky and colleagues warned that "prescribing and administering growth hormone has become a routine intervention in an industry that is variably called 'antiaging,' 'regenerative,' 'longevity' or 'age management' medicine.''

The authors said that "increased cancer risk" was a concern with longterm use of the hormone, and that higher levels of insulin-like growth factor -- the key chemical stimulated by human growth hormone -- is linked to tumors in mice.

Human growth hormone is also linked to diabetes, tissue swelling and carpel tunnel syndrome.

Dr. Shlomo Melmed, president of the International Society of Endocrinologists, said that prescribing human growth hormone to adults for any condition but AIDS-related wasting or rare pituitary disorders is "illegal, and inappropriate medically.''

At a cost approaching $10,000 a year, Melmed said the taking of human growth hormone is a waste of medical resources. "There is no proof it works for what we buy it for, and it may not be safe,'' he said. "It adds to the economic burden of our health care system, and unnecessarily.''

E-mail Sabin Russell at srussell@sfchronicle.com.

Genetically Engineered Anti-Aging Medication (HGH) Poses Undisclosed Cancer Risks, Warns Samuel S. Epstein, M.D.

Use of the genetically engineered human growth hormone (HGH) for anti-aging medication has become a major growth industry. Suppliers of HGH, including those offering mail order prescriptions, are proliferating on websites and the Internet. The Chicago-based seven-year-old American Academy of Anti-Aging Medicine, with over 8000 members, promotes injectable HGH in programs claiming to stop or even reverse aging, including decreasing body fat, and increasing muscle mass and bone density. However, practitioners of this burgeoning "health" industry are either ignorant of or suppress well-documented information on the grave cancer risks of HGH medication.

HGH induces growth promoting and other effects by stimulating the liver to increase production of the natural Insulin-like Growth Factor-1 (IGF-1) whose blood levels normally decline with advancing age. However, there are numerous publications in prestigious peer reviewed scientific journals showing that elevated IGF-1 levels are strongly associated with major excess risks of colon, prostate, and breast cancers; even minor elevations are associated with up to 7-fold increased risks of breast cancer, risks almost as high as those in women carrying genes (BRCA1 and BRCA2) with the strongest hereditary predisposition. Additionally, IGF-1 inhibits the programmed self-destruction (apoptosis) of cancer cells, thus stimulating the growth and invasiveness of small, undiagnosed cancers, besides increasing the resistance of cancers to chemotherapy. For these reasons, anti-aging HGH medication, compounded by failure to explicitly disclose its grave risks, constitutes medical malpractice.

Learn more about IGF-1

There are also growing concerns on possible risks from the use of HGH nutritional supplements, including oral sprays. It should, however, be recognized that HGH absorption from the mouth and gut is unlikely to be significant, in striking contrast to complete absorption from injectable medication. Nevertheless, nutritional HGH supplements should be phased out until it can be shown that they do not elevate blood IGF-1 levels.

HGH medication should only be used by qualified endocrinologists for highly restricted medical disorders, such as dwarfism due to pituitary gland deficiency, as approved by the FDA in 1985; anti-aging medication has never received such approval.

Source: Cancer Prevention Coalition Press Release – March 14, 2000

CONTACT:
Samuel S. Epstein, M.D.

Chairman, Cancer Prevention Coalition

c/o University of Illinois at Chicago

School of Public Health, M/C 922

2121 W. Taylor Street
Chicago, IL 60612

312-996-2297

epstein@uic.edu

Growth Horm IGF Res.

2006 Oct-Dec;16(5-6):277-89.

The oncogenic potential of growth hormone.

· Perry JK, Emerald BS, Mertani HC, Lobie PE.

The Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, 2-6 Park Avenue, Grafton, Private Bag 92019, Auckland 1023, New Zealand.

A growing body of recent literature indicates that in addition to an essential role in growth and development, growth hormone may also play a more sinister role in oncogenic transformation and neoplastic progression. Here we review the accumulating evidence implicating growth hormone in the development and progression of cancer and describe what is known of the mechanisms utilized by this hormone in neoplastic transformation.

Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):14992-3. Epub 2004 Oct 12.

The oncogenic potential of autocrine human growth hormone in breast cancer.

Institute for Molecular Biosciences, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. m.waters@imb.uq.edu.au

Lancet. 2004 Apr 24;363(9418):1346-53.

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

Science Daily — WINSTON-SALEM, N.C. Deficiencies of growth hormone and similar compounds may reduce cancer and kidney disease late in life, but also may lead to cartilage degeneration and impaired memory and learning ability, according to research at Wake Forest University Baptist Medical Center and four other institutions.

The researchers used a rat model to explore the effects of growth hormone and another compound, IGF-1 (insulin-like growth factor 1) on adult rats and found paradoxical effects, according to William E. Sonntag, Ph.D., professor of physiology and pharmacology at Wake Forest University Baptist Medical Center and the lead investigator.

"Things that happen when you are an adolescent may have an impact on how long you live and what you die of," he said.

"The presence of growth hormone and IGF-1 is necessary for maintenance of cognitive function and prevention of cartilage degeneration," Sonntag and his colleagues reported in an article in Endocrinology, published on-line today.

But the hormones also increase cancer and other diseases that limit lifespan.

The group also found that "cartilage degeneration that normally accompanies aging is accelerated by the absence of growth hormone."

Note: This story has been adapted from a news release issued by Wake Forest University Baptist Medical Center.

Cancer and insulinlike growth factorI

A potential mechanism linking the environment with cancer risk
Insulinlike growth factor-I acts as an important mediator between growth hormone and growth throughout fetal and childhood development. Its effects and those of the other insulinlike growth factors are modulated by at least six different binding proteins.

The role of insulinlike growth factor-I in promoting cancer has been investigated for many years, but recently

the quality and quantity of evidence has increased.¹ In particular, a number of prospective studies using stored blood collected up to 14 years before the onset of disease have shown associations between insulinlike growth factor -I and prostate cancer, premenopausal breast cancer, and colon cancer.^2–4

The risk of cancer is higher among people with raised concentrations of insulinlike growth factor-I, and it is lower among those with high concentrations of insulinlike growth factor binding protein3 (the main binding protein). The associations are similar when people whose blood samples were taken soon before diagnosis are excluded from analyses, suggesting that the observed relations are not due to the release of the growth factor by preclinical cancers.^2–4 The effects are sizeable and stronger than the effects seen in relation to

most previously reported risk factors.1 Weaker evidence from casecontrol studies suggests that the ratio of

insulinlike growth factorI to insulinlike growth factor binding protein3 may also be related to the risk of childhood leukaemia and lung cancer.5 6 The increasing direct epidemiological evidence that relates insulinlike growth factorI to the risk of cancer is consistent with more circumstantial evidence.

Acromegaly, in which high concentrations of growth hormone stimulate production of high concentrations

of insulinlike growth factorI, has been associated with an increased risk of colorectal cancer and breast cancer in some studies and less consistently with prostate, thyroid, and haematological malignancies.7 In many studies anthropometric markers of the activity of insulinlike growth factorI, such as height and leg

length, are associated with cancer incidence, particularly with the cancers for which risk increases with rising concentrations of insulinlike growth factorI.8 While adult height is not strongly associated with concentrations of insulinlike growth factorI in cross sectional studies, it may be a marker for this growth factor during childhood growth,9 and this may be the period during which it acts to increase the risk of cancer occurring in later life.3 Additionally, animal studies have shown that high overall intake of energy in early postnatal life is associated with an increased cancer risk, and this association has recently been found in humans.10 In animals, calorie restriction reduces the risk of cancer primarily by reducing the circulating

concentrations of insulinlike growth factorI.11 Support for the link between cancer and this growth factor comes from an understanding of the potential mechanisms. Concentrations of insulinlike growth factorI could be a surrogate for the activity of sex steroid hormones, which in turn influence the risk of cancer. However, associations between insulinlike growth factorI and cancers dependent on sex hormones are stronger than those between directly measured concentrations of sex hormones and these cancers. Insulinlike growth factorI may increase cell turnover and the susceptibility of cells to malignant transformation both directly and by modulating the effects of sex steroids. The fact that the risk associated with increased concentrations of insulinlike growth factorI is greater in people whose DNA is more susceptible to damage induced by mutagens supports this suggestion.6 Alternatively, insulinlike growth factorI might increase the risk of cancer through its antiapoptotic activity.1 In this case it prevents the programmed death of cells that have been transformed thus interrupting an important process which retards the development of cancer. Experiments using animal and cell cultures have shown that the antiapoptotic activity of insulinlike growth factorI is counterbal anced by the activity of insulinlike growth factor binding protein3, which may have a direct and independ ent stimulatory action on apoptosis.
Given the increasing evidence of the risk of cancer, caution should be exercised in the exogenous use of either insulinlike growth factorI or substances that increase concentrations of it. Despite supposedly being restricted to use only in licensed applications, growth hormone is easily available as an antiageing treatment and is surprisingly widely used by athletes and body builders, who also use insulinlike growth factorI. Those who use these products are unlikely to be aware of their potentially harmful effects. The final accounting on the balance sheet of growth hormone, insulinlike growth factorI, and chronic disease is uncertain. The increasing evidence of a risk of cancer may be counterbalanced by a protective effect on the risk of cardiovascular disease. Growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased risk of mortality from cardiovascular disease.12 Low concentrations of insulinlike growth factorI are also associated with cardiovascular morbidity in the elderly.13 Furthermore, the same studies that have shown a positive association between height and cancer risk suggest that greater height is associated with decreases in cardiovascular and all cause mortality.14

The predictive value of insulinlike growth factorI may be useful in screening for cancer. For example, the

ratio of insulinlike growth factorI to prostate specific antigen may be a better predictor of the development of prostate cancer than the antigen alone.15 Growth hormone antagonists are being investigated as treat

ments for some cancers and chemotherapeutic agents are being developed to block the activity of insulinlike

growth factorI or to promote the activity of insulinlike growth factor binding protein3; these agents may offer

additional ways of stimulating apoptosis in malignantly transformed cells. Lastly, better knowledge of the factors that influence overall concentrations of insulinlike growth factorI may help in devising strategies to

prevent cancer at a population level. Much recent attention has focused on the human genome project and its potential for unravelling the causes of cancer. The genes that have been identified as causing cancer so far account for only a small proportion of major cancers. The rapid and sizeable changes in the incidence of cancer that have been seen during times of economic development coupled with the findings from twin studies—which compare the concordance of cancer risk in identical and nonidentical twins to determine the relative influence of genetic and environmental factors—both point to the importance of nongenomic factors.16 The new epidemiological find ings about insulinlike growth factorI provide one potential mechanism through which an array of previously identified environmental risk factors may act.

George Davey Smith professor, clinical epidemiology

David Gunnell senior lecturer, epidemiology and public health

Department of Social Medicine, University of Bristol, Bristol BS8 2PR

Jeff Holly professor, clinical science

Department of Surgery, University of Bristol

1 Holly JMP, Gunnell DJ, Davey Smith G. Growth hormone, IGFI and cancer. Less intervention to avoid cancer? More intervention to prevent cancer? J Endocrinol 1999;162:32130.

2 Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, et al. Plasma insulinlike growth factorI and prostate cancer risk: a prospective study. Science 1998;279:5636.

3 Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulinlike growth factorI and risk of breast cancer. Lancet 1998;351:13936.

4 Ma P, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulinlike growth factor (IGF)I and IGFbinding protein3. J NatlCancer Inst 1999;91:6205.

5 Petridou E, Dessypris N, Spanos E, Mantzoros C, Skalkidou A, Kalmanti M, et al. Insulinlike growth factorI and binding protein3 in relation to childhood leukaemia. Int J Cancer 1999;80:4946.

6 Wu X, Yu H, Amos CI, Hong WK, Spitz MR. Joint effect of insulinlike growth factors and mutagen sensitivity in lung cancer risk. J Natl Cancer Inst 2000;92:73743.

7 Jenkins P. Cancer in acromegaly. Trends Endocrinology Metab 1998;9:3606.

8 Gunnell D. Height, insulinlike growth factors and cancer risk. Growth Horm IGF Res 2000;10(suppl A):3940S.

9 Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al. Serum insulinlike growth factorI in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78:74452.

10 Frankel S, Gunnell DJ, Peters TJ, Maynard M, Davey Smith G. Childhood energy intake and adult mortality from cancer: the Boyd Orr cohort study. BMJ 1998;316:499504.

11 Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, et al. Dietary restriction reduces insulinlike growth factor I levels, which modulated apoptosis, cell proliferation, and tumor progression in p53defieicnt mice. Cancer Res 1997;57:466772.

12 Sacca L, Cittadine A, Fazio S. Growth hormone and the heart. Endocr Rev 1994;15:55573.

13 Janssen JAMJL, Stolk RP, Pols HAP, Grobbe DE, Lamberts SWJ. Serum total IGFI, free IGFI and IGFBP1 levels in an elderly population. Relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol 1998;18:27782.

14 Davey Smith G, Hart C, Upton M, Hole D, Gillis C, Watt G, et al. Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory and cancer mortality. J Epidemiol Commun Health 2000;54:97103.

15 Djavan B, Bursa B, Seitz C, Soeregi G, Remzi M, Basharkhah A, et al. Insulinlike growth factorI (IGFI), IGFI density and IGF/PSA ratio for prostate cancer detection. Urology 1999;54:6036.

16 Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl

J Med 2000;343:7885.

Editorials

848 BMJ VOLUME 321 7 OCTOBER 2000 bmj.com

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GROWTH HORMONE/ HGH/ANTIAGING AND SPORTS

Thomas Perls MD, MPH, FACP

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Hormone thought to slow aging associated with increased risk of cancer death

Hormone link to cancer
from The Courier Mail
Bernadette Condren

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

GROWTH HORMONE/ HGH/ANTIAGING AND SPORTS

Thomas Perls MD, MPH, FACP

Home

What is the law?

FDA Alerts Warnings

Clinics

Disciplined Doctors

Pharmacies in Trouble

Docs dying young

Entertainers

FDA Letters and Alerts

Police, Firemen, Military

Bodybuilders & Wrestlers

Anti-Aging Industry

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Shortens Life Span!

Cancer

Side Effects

Pharma $$$

International Cases

GH In The News

Bioidenticals Supplements

Anti-aging & Quack Signs

Steroids

Sports and Athletes Dying

Helpful Links

Contact Dr. Perls

Hormone thought to slow aging associated with increased risk of cancer death

Hormone link to cancerfrom The Courier MailBernadette Condren

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

Deficiency Of Growth Hormone And IGF-1 Reduces Cancer And Kidney Disease, But Creates Other Problems

Hormone link to cancer
from The Courier Mail
Bernadette Condren