GHR15 and the Prostate

Insulin-like 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.

L. Cass Terry, M.D., Ph.D., Pharm.D.,
Medical College of Wisconsin, Milwaukee, WI. 53226
Chief Medical Officer, Cenegenics.

IGF1, 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 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.