and the Prostate
Growth Factor-1 (IGF1, Somatomedin C) Blood Levels Are Not Associated
With Prostate Specific Antigen (PSA) Levels or Prostate Cancer:
A Study of 749 patients.
Cass Terry, M.D., Ph.D., Pharm.D.,
Medical College of Wisconsin, Milwaukee, WI. 53226
Chief Medical Officer, Cenegenics.
also known as somatomedin C, is 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
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.
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.
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:
line analysis showed no correlation between IGF1 and PSA levels.
data were then grouped by normal (<4.1 ng/ml) and abnormal
(>4.0 ng/ml) PSA levels, resulting in the data below:
this case, the mean IGF1 levels were essentially the same, even
though the median PSA in the abnormal group was six times higher.
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).
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.