Insulin, IGF, GH and cancer

[lookinfit75]

This study would seem to implicate the BB lifestyle as a direct cause of cancer.

I get a number of alerts for new journal articles sent to me. I got this one yesterday.

Study protocol: Insulin and its role in cancer
BMC Endocrine Disorders 2007,

7:10 doi:10.1186/1472-6823-7-10


K Harish ([email protected])
M Dharmalingam ([email protected])
M Himanshu ([email protected])


ISSN 1472-6823
Article type Study protocol
Submission date 16 July 2007
Acceptance date 22 October 2007
Publication date 22 October 2007
Article URL http://www.biomedcentral.com/1472-


Abstract
Background: Studies have shown that metabolic syndrome and its consequent
biochemical derangements in the various phases of diabetes may contribute to
carcinogenesis. A part of this carcinogenic effect could be attributed to
hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding
proteins and hence increase levels of free IGF-1.

It is well established that bioactivity
of free insulin growth factor 1 (IGF-1) increases tumor turnover rate.

The objective is
to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying
the relation between insulin resistance/sensitivity and IGF-1 levels in cancer
patients. We postulate that hyperinsulinaemia which prevails during initial phases of
insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-
1, which may contribute to process of carcinogenesis.


Methods / Design: Based on our pilot study results and power analysis of the same,
we have designed a two group case-control study. 800 proven untreated cancer
patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200
healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1
levels shall be determined in all subjects. Association between the two parameters
shall be tested using suitable statistical methods.


Discussion: Well controlled studies in humans are essential to study the link
between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study
could provide insights to the role of insulin, insulin resistance, IGF-1 in
carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve
around insulin and insulin resistance.

Background

The association of diabetes mellitus and cancer has been reported more than 100
years ago [1]. Population studies have shown increased evidence of this
association.

Diabetes has been recognized as a risk factor for development of
breast, endometrial, colorectal and pancreatic carcinomas [2]. Breast, endometrial,
colorectal and pancreatic carcinomas are best studied with regard to their
association with diabetes/insulin resistance. Population studies have shown that the
effects of diabetes mellitus on colorectal cancer may be mediated through
mechanisms ranging from increased colonic transit time to hyperinsulinaemia. In
relation to the latter, at least in the early phase of development, type 2 diabetes
mellitus is associated with increased circulating insulin concentrations [3, 4]. A large
cohort study concluded that diabetes is associated with a modestly increased risk for
endometrial cancer among women [5]. Future research, particularly prospective
studies with biological samples, could be very helpful in answering questions aimed
at clarifying these mechanisms [5]. Data suggest that type 2 diabetes might be
associated with up to 10–20% excess risk for breast cancer and that it could also
have detrimental effects on the natural history, diagnosis, and treatment of breast
cancer [1, 6].

In the past few years both laboratory investigations and population studies have
provided some circumstantial evidence that insulin growth factor biochemical derangements may contribute to carcinogenesis.

Several studies
implicate hyperinsulinism, a condition that prevails prior to the onset of diabetes (part
of metabolic syndrome) as candidate mediator in carcinogenesis [10].

Studies have
revealed that high levels of circulating insulin decreases levels of insulin like growth
factor binding protein 1 and 3 (IGFBP 1,3). Thus free IGF-1 levels increase in
circulation [11, 12].

Another aspect of IGF physiology is the IGF signaling. In this
signaling process, IGF-1 receptor is a predominant factor and is crucial for tumor
transformation and survival of malignant cell. It has comparatively less role in normal
cell growth [13].
Thus role of IGF-1 in promoting carcinogenesis and its prognosis is
well established. Over the recent years, IGF-1 physiology has been widely studied.
The IGF system, comprises of insulin-like IGF-I, IGF-II, and IGFBPs. IGF-1 as a
growth factor plays a dominant role over IGF-2 and hence is widely studied.

Until
recently, growth hormone was the only known stimulant of IGF-1 production.
Different lines of evidence suggest that the IGF/IGFBP system may be regulated by
factors other than growth hormones. States of nutritional deprivation, such as
starvation and protein caloric under-nutrition and type 1 diabetes mellitus, in animal
models have long been known to influence the production of IGFs [14-16]. Various
studies have shown that resistance to insulin action, as found in diabetic patients,
has been associated with an increase IGFBP-3 protease activity, there by reducing
IGFBP-3 levels [17]. Also, Insulin increases IGF-I bioavailability through IGFBP-1
suppression [14, 18, 19]. Thus there is ample evidence to suggest that insulin
resistant states increase free IGF-1 levels.

Medical literature suggests that well controlled biochemical and genetic studies are
required to establish the link between insulin, IGF-1, diabetes and cancer. We
propose to investigate the role of hyperinsulinemia in carcinogenesis.

The primary objective of the study is to investigate the role of insulin resistance or
sensitivity in carcinogenesis.

This is done by studying the relation between insulin
resistance/sensitivity and IGF-1 levels in cancer patients. The secondary objective is
to study the above mentioned association with organ specific cancers if possible.
Carcinogenesis is multi-factorial.


The metabolic and genetic derangements that take
place during carcinogenesis may be induced by carcinogens and inherited genetic
factors. The role of either could be variable in a given case. We hypothesize that
people with insulin resistance are at risk of developing cancer due to high levels of
circulating IGF-1. Such a risk would increase if other such factors are prevalent /
acquired. A person with high levels of IGF-1 may be predisposed to cancer and
his/her risk of developing cancer would increase with the presence of other such
factors. Cancer being a non-communicable disease, with multiple risk factors,
modifiable risk factors are very few.

Controlling hyperinsulinaemia would modify one
major risk factor. IGF-1 levels in body change with age. In addition, riskIGF-1 has high bioactivity on epithelial cells. Thus their role in carcinomas is of
significance rather than other types of malignancies. Hence we limit our study to
carcinomas of breast, GIT, liver, prostate, uterus, cervix and ovaries.

 

[Tatyana]

This study would seem to implicate the BB lifestyle as a direct cause of cancer.

I am not following you unless you assert that a BBing lifestyle has to include performance enhancing drugs like GH, IGF-1 and insulin.

If this is not what you mean, please elaborate.

I have a few other abstracts that may be of interest.

I would also like to add that while it is known that the growth factor/growth factor signalling pathway is known to be out of control in quite a few cancers, what actually causes this, uncertain.

It does seem like with everything in life, I do think it is all about moderation, getting the balance right.



Accession number & update
17349798 Medline 20070401.

Title

Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

Source

Pharmacological research : the official journal of the Italian Pharmacological Society, {Pharmacol-Res}, May 2007 (epub: 03 Feb 2007) , vol. 55, no. 5, p. 359-69, 119 refs, ISSN: 1043-6618.

Author(s)

Tentori-Lucio, Graziani-Grazia.
Author affiliation
Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. [email protected].

Abstract

Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports.

Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agentswith the aim to improve appearance or to counteract ageing.

Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers.

Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion.

More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness.

Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time.

Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

 

[lookinfit75]

I should have written that differently. It would seem that "professional" BB or at least those professionals that use large amounts of GH, insuline, and IGF are prone to cancer, according the study you posted. Does that make better sense?
Obviously if you are a recreational BB and user of AAS then the chances are less likely because the amounts a recreational user uses are far less than those a pro level BB would use, in a eutopic society of course. A recreational BB/user would more than likely not have a need of insulin. Maybe a little GH but the others are categorized as more exotic drugs that are quite dangerous if not taken correctly.

 

[Tatyana]

I think a lot of things in excess throw off the bodies homeostasis, making it more prone to pathogenic processes.

Cancer is multi-factorial, and it is also going to depend on the individuals genetics.

Doctors are not meant to prescribe GH or IGF-1 to ANY patients if they have any sort of cancers going on.

Too much sun, melanoma, too little sun, there are other cancer risks, too much red meat with other factors and no exercise, cancer risk, red meat/animal with diet of fruit and veggies, great for building muscle and good lipid profiles..........

We actually have cancer cells arising all the time, our Natural Killer cells and cyto toxic T cells kill them off.

However, there maybe a risk when you are introducing even more growth factors into your body.

I love this phrase I once heard from a Buddhist monk, the poison is all in the dosage.

 

[DBBT]

sweet!

 

[lookinfit75]

Of course, moderation is the key (IN EVER ASPECT OF ONE'S LIFE FOR THAT MATTER) and for certain people, they just cannot partake of these drugs. Too bad many people don't heed that warning.
I like the Buddhist quote you posted. Truer words have never been spoken.

 

[FIRE FIGHTER614]

very good post !!!

 

[Strategus]

"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison…." Paracelsus (1493-1541)

http://learn.caim.yale.edu/chemsafe/references/dose.html

Sunlight is a very good example. Too much sun can induce melanoma or other skin cancers...but too little sun/vitamin D is correlated with higher occurrence of prostate cancer and also breast cancer in women in the Northeast where there is low sunlight from late October-March.

http://www.ajph.org/cgi/content/full/96/2/252

"Generally, exercise's beneficial effects in the context of aging and longevity are best observed with moderate and repeated bouts of exercise interrupted by a period of normal life activity."

Just doing exercise causes the generation of reactive oxygen species (toxic in large quantities but stimulating in small quantities) in tissue. There is a reason that people usually w/o for an hour or so, rather than the 4-5 h that leads to catabolism.

You guys might enjoy this article.

http://www.scipub.org/fulltext/AJPT/AJPT3127-40.pdf

I don't have specific info on IGF-1 or non-diabetics using insulin, but these articles are relevant to the general concept of 'moderation.'

 

[canadianhitman]

The rule of thumb I've always heard is that IGF can't give you cancer....but....if you've already got cancerous cells, it will speed the progression.