Insulin-like Growth Factor-1 (IGF-1, Somatomedin C) Blood Levels Are Not
Associated With Prostate Specific Antigen (PSA) Levels or Prostate Cancer: A Study of 749
patients.
L. Cass Terry, M.D., Ph.D., Pharm.D.,
Medical College of Wisconsin, Milwaukee, WI. 53226
Chief Medical Officer, Cenegenics.
IGF-1, also known as somatomedin
C, is a polypeptide hormone about the same size as insulin. It is produced
predominantly in the liver in response to growth hormone (GH) release from the
pituitary gland. Many of the growth promoting effects of GH are due to its ability to
release IGF1 from the liver, which in turn acts on several different tissues to enhance
growth. IGF1 belongs in the ‘superfamily’ of substances known as ‘growth
factors,’ along with epidermal, transforming, platelet derived, fibroblast, nerve,
and ciliary neurotrophic growth factors. These agents have in common the ability to
stimulate cell division, known as mitogenesis, and cell differentiation. Because IGF1 is
mitogenic to prostate epithelial cells, as well as other cell lines in tissue
culture, its role, if any, in prostate cancer has been considered and raises the
question as to whether higher levels of circulating IGF1 might increase the risk of
prostate cancer. The best and most sensitive screening test available for prostate cancer
is prostate specific antigen (PSA), a serine protease secreted by prostate
epithelial cells.
The incidence of prostate cancer increases with age in men, whereas, blood levels of
IGF1 decline significantly with age, about 14% per decade after age 30. It therefore
seemed unlikely that IGF1 would have any causative relationship with prostate cancer,
however, it does raise the question as to whether supplementation with recombinant
human GH (rhGH), as a deterrent to the aging process, might increase the risk.
The purpose of this study was to determine whether IGF1 blood levels in men receiving
rhGH supplementation had any relationship to blood PSA levels, as an indicator of prostate
cancer. To accomplish this goal, PSA and IGF1 levels were measured in 749 blood
samples from men with ages ranging from 22 to 86 years old, many of whom were on rhGH
replacement therapy. Age, IGF1, and PSA were matched in 544 individuals. Also, IGF1 levels
were measured in 6 patients with known prostate cancer, prior to rhGH administration.
The mean age of all men was 55.1 + 0.5 yr. with a median of 55 and mode of 64.
Mean PSA was 2.2 + 0.1 ng/ml with a median of 1.1, mode of 0.7, and range of <0
to 63.7. Trend line analysis demonstrated a clear increase in PSA levels with increasing
age, as expected. Mean IGF1 was 218.8 + 3.4 ng/ml with a median of 211, mode of
183, and range of 20 to 498. There was no correlation between IGF1 and PSA levels. IGF1
levels were further broken down into quartiles and compared with PSA levels in each. This
resulted in the following data:
| |
25%ile |
50%ile |
75%ile |
100%ile |
Mean IGF1
(ng/ml) |
122 |
187 |
239 |
331 |
| Range |
(20-159) |
(160-211) |
(212-271) |
(272-518) |
Median PSA
(ng/ml) |
1.1 |
0.9 |
1.0 |
1.1 |
| Range |
(<0-61.7) |
(0.2-27.5) |
(<0-8.6) |
(0-25.2) |
| Sample Size |
138 |
133 |
138 |
135 |
 |
Trend line analysis showed no correlation between IGF1 and PSA levels.
The data were then grouped by normal (<4.1 ng/ml) and abnormal (>4.0 ng/ml) PSA
levels, resulting in the data below:
| |
PSA >4.0 |
PSA <4.1 |
Mean IGF1
(ng/ml) |
218 |
219 |
| Range |
(20-456) |
(22-518) |
Median PSA
(ng/ml) |
6.0 |
0.9 |
| Range |
(4.1-61.7) |
(<0-4.1) |
| Sample Size |
59 |
536 |
  |
In this case, the mean IGF1 levels were essentially the same, even though the median
PSA in the abnormal group was six times higher.
Also, the mean IGF1 level, before rhGH treatment, in 6 cases of known prostate cancer
was 121.5 + 30.0 ng/ml, which places this group in the lowest quartile of IGF1
levels, regardless of age. Taken together, the data provide strong evidence that blood
IGF1 levels have no relationship with PSA levels or prostate cancer. The results are in
agreement with those of several other investigators (Ho, P. & Baxter, RC, Clin
Endocrinol 46, 145-154, 1997; Cohen, P. et al., J Clin Endocrinol Metab 76:1031-1035,
1993; Kanety, H. et al., J Clin Endocrinol Metab 77:229-233, 1993). A recent paper (Chan,
JM et al., Science 279:563-566, 1998) suggests that there is an association between
circulating levels of IGF1 and prostate cancer; however, IGF1 levels were measured an
average of 7 years before the diagnosis of prostate cancer and not at the time of
diagnosis. Furthermore, there was no increase found in prostate cancer, or any other
malignancy, in approximately 3000 patients during long term treatment with rhGH
(Bengt-Ake Bengtsson, personal communication).
Conclusion: Circulating IGF1 levels have no relationship to prostate cancer and are
not a risk factor in patients, with or without rhGH administration. In other words, there
is no evidence that rhGH replacement to deter aging carries any increased risk for
prostate cancer.
*Thanks to Dr. Ron Klatz for this "newstidbit" from his web
site http://worldhealth.net
