Several substances such as growth hormone (GH), erythropoietin (Epo), and anabolic steroids (AS) are improperly utilized to increase the performance of athletes. Evaluating the potential cancer risk associated with doping agents is difficult since these drugs are often used at very high doses and in combination with other licit or illicit drugs.
The GH, via its mediator, the insulin-like growth factor 1 (IGF-1), is involved in the development and progression of cancer. Animal studies suggested that high levels of GH/IGF-1 increase progression of androgen-independent prostate cancer. Clinical data regarding prostate cancer are mostly based on epidemiological studies or indirect data such as IGF-1 high levels in patients with prostate cancer. Even if experimental studies showed a correlation between Epo and cancer, no clinical data are currently available on cancer development related to Epo as a doping agent. Androgens are involved in prostate carcinogenesis modulating genes that regulate cell proliferation, apoptosis and angiogenesis. Most information on AS is anecdotal (case reports on prostate, kidney and testicular cancers). Prospective epidemiologic studies failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk.
Currently, clinical and epidemiological studies supporting association between doping and urological neoplasias are not available. Nowadays, exposure to doping agents starts more prematurely with a consequent longer exposition period; drugs are often used at very high doses and in combination with other licit or illicit drugs. Due to all these elements it is impossible to predict all the side effects, including cancer; more detailed studies are therefore necessary.
GoldmanB.Liver carcinoma in an athlete. Ann. Int.Med.1984; 100: 158–159.
9.
OverlyW.L., DankoffJ.A., WangB.K., SinghU.D.Androgens and hepatocellular carcinoma in an athlete.Ann Int Med1984; 100: 158–159.
10.
CreaghT.M., RubinA., EvansD.J.Hepatic tumours induced by anabolic steroids in an athlete.J Clin Pathol1988; 41: 441–443.
11.
BagiaS., EwuittP.M., MorrisD.L.Anabolic steroid-induced hepatic adenomas with spontaneous haemorrhagie in a body builder.Aus NZJ Surg2000; 70: 686–687.
12.
SocasL., ZumbadoM., Perz-LuzardoO.Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature.Br J Sports Med2005; 39: e27.
13.
SnyderP.J.Androgens. In: BruntonL.L., LazoJ.S., ParkerK.L., editors. The pharmacological basis of therapeutics.11th ed.New York: Goodman & Gilman's; 2005. p. 1573–1585.
RobertsJ.T., EssenighD.M.Adenocarcinoma of prostate in 40-years old body-builder.Lancet1986; 2: 742.
20.
StreetC., AntonioJ., CudlippD.Androgen use by athletes: a reevaluation of the health risks.Can J Appl Physiol1996; 21: 421–440.
21.
FroehnerM., FischerR., LeikeS., HakenbergO.W., NoackB., WirthM.P.Intratesticular leiomyosarcoma in a young man after high dose doping with oral-turinabol. A case report.Cancer1999; 86: 1571–1575.
22.
ParsinenM., KujalaU., VartiainenE., SarnaS., SeppalaT.Increased premature mortality of competitive powerlifters aspected to have used anabolic agents.Int J Sports Med2000; 21: 225–227.
23.
EmermanJ.T., LeahyM., GoutP.W., BruchovskyN.Elevated growth hormone levels in sera from breast cancer patients.Horm Metab Res1985; 16: 421–424.
24.
PeyratJ.B., BonneterreJ., HecquetB.Plasma insuline-like growth factor 1 (IGF-1) concentrations in human breast cancer.Eur J Cancer1993; 29A: 492–497.
25.
HankinsonS.E., WilletW.C., ColditzG.A.Circulating concentrations of insuline-like growth factot 1 and risk of breast cancer.Lancet1998; 351: 1393–1396.
26.
ChanJ.M., StampferM.J., GiovannucciE.Plasma insuline-like growth factor 1 and prostate cancer risk: a prospective study.Science1998; 279: 563–566.
27.
YuH., SpitzM.R., MistryJ., GuJ., HongW.K., WuX.Plasma levels of insuline-like growth factor 1 and lung cancer risk: a case-control study.J Natl Cancer Inst1999; 91: 151–156.
28.
MaJ., PollakM.N., GiovannucciE.Prospective study of colorectal cancer risk in men and plasma levels of insuline-like growth factor (IGF-1) and IGF-binding protein-3, J Natl Cancer Inst1999; 91: 620–625.
29.
JenkinsP.J., besserM.Clinical perspective: acromegaly and cancer, a problem.J Clin Endocr and Metab2001; 86: 2935–2941.
OgilvieM., YuX., Nicolas-MetralV.Erythropietin stimulates proliferation and interferes with differentiation of myoblasts.J Biol Chem2000; 275: 39754–39761.
GaudardA., Varlet-MarieE., BressolleF., AudranM.Drugs for increasing oxygen and their potential use in doping: a review.Sports Med2003; 33: 187–212.
34.
JelkmannW.Use of recombinant human erythropoietin as an antianemic and performance enhancing drug.Curr Pharm Biotechnol2000; 1: 11–31.
35.
LarssonO., GirnitaA., GirnitaL.Role of insuline-like growth factor 1 receptor signalling in cancer.Br J Cancer2005; 92: 2097–2101.
36.
MitsiadesC.S., MitsiadesN.Treatment of hematologic malignancies and solid tumors by inhibiting IGF receptor sgnaling.Expert Rev Anticancer Ther2005; 5: 487–499.
37.
AkagiY., LiuW., ZebrowskyB., XieK., EllisL.M.Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-1.Cancer Res1998; 58: 4008–4014.
38.
TornellJ., CarlssonB., PohjanenP., WennboH., RymoL., IsakssonO.High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice.J Steroid Biochem Biol1992; 43: 237–242.
39.
WuJ.D., HaugkK., WoodkeL., NelsonP., ColemanI., PlymateS.R.Interaction of IGF signalling and the androgen receptor in prostate cancer progression.J Cell Biochem2006; 99: 392–401.
40.
BurtrumD., ZhuZ., LuD.A fully human monoclonal antibody to the insuline-like growth factor I receptor blocks ligant-depent signalling and inhibits human tumor growth in vivo.Cancer Res2003; 63: 8912–8921.
41.
JenkinsP.J., MukherjeeA., ShaletS.M.Does growth hormone cause cancer?Clin Endocrinol2006; 64: 115–121.
42.
MillsJ.L., SchnbergerL.B., WysowskyD.K.Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients.J Pediatr2004; 144: 430–436.
43.
SvenssonJ., BengtssonB.A., RosenT., OdenA., JohanssonG.Malignant disease and cardiovascular morbidity in hypopitutary adults with or without growth hormone replacement therapy.J Clin Endocrinol Metab2004; 89: 3306–3312.
44.
HardeeM.E., ArcasoyM.O., BlachwellK.L., KirkpatrickJ.P., DewhirstM.W.Erythropoietin biology in cancer.Clin Cancer Res2006; 12: 332–339.
45.
YasudaY., FujitaY., MatsuoT.Erythropietin regulates tumor growth of human malignancies.Carcinogenesis2003; 24: 1021–1029.
46.
CarliniRG, DussoAS; ObilaoC.I., AlvarezU.M., RothsteinM.Recombinant human erythropietin (rHuEPO) increases endothelin-1 release by endothelial cells.Kidney Int1993; 43: 1010–1014.
47.
HenkeM., LaszigR., RubeC.Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomized, doubleblind, placebo-controlled trial.Lancet2003; 362: 1255–1260.
48.
Leyland-JonesB., SemiglazovV., PawlickiM.Maintaining normal haemoglobin levels with epoietin a in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study.J Clin Oncol2005; 23: 5960–5972.
49.
MichaelU., JackischC., LenhardM.S.Epoietin-alpha reduces red blood cell transfusion (RBC) in high risk breast cancer patients with adjuvant dose-dense, sequential chemotherapy with epirubicin (E), paclitaxel (T) and cycolphosphamide (ETC). 41 st Annual Meeting of the American Society of Clinical Oncology, May 13–17, 2003.J Clin Oncol2005; 23: 613 (Abstract).
50.
BlohmerJ.U., WurschmidF., PetryU., WeiseG., SehouliJ., KimmingR.Results with sequential adjuvant chemo-radiotherapy with vs without epoietin alfa for patients with high risk cervical cancer: results of a prospective, randomized, open and controlled AGO- and NOGGO-intergropup study. 29th European Society for Medical Oncology Congress, 29 October to 2 November 2004.Ann Oncol2004; 15(Suppl. 3): 447 PD (Abstract).
51.
ThiblinI., PeterssonA.Pharmacoepidemiology of anabolic androgenic steroids: a review.Fundam Clin Pharmacol2005; 19: 27–44.
52.
DehmS.M., TindallD.J.Molecular regulation of androgen action in prostate cancer.J Cell Biochem2006; 99: 333–344.
53.
MabjeeshN.J., WillardM.T., FredericksonC.E., ZhongH., SimonsJ.W.Androgens stimulate hypoxia-inducible factor 1 activation via autocrine loop of tyrosine kinase receptor/phosphatidylinositol 3'-kinase/protein kinase B in prostate cancer cells.Clin Cancer Res2003; 9: 2416–2425.
54.
MayerD., ForstnerK.Impact of dehydroepiandrosterone on hepatocarcinogenesis in the rat.Int J Oncol2004; 25: 1021–1030.
55.
LeungG., TsaoS.W., WongY.C.Sex hormone-induced mammary carcinogenesis in female Noble rats: detection of differentially expressed genes.Breast Cancer Res Treat2003; 77: 49–63.
BronsonF.H., MatherneC.M.Exposure to anabolic-androgenic steroids shortenes life span of male mice.Med Sci Sports Exerc1997; 29: 615–619.
58.
SeveriG., MorrisH.A., MacInnisR.J.Circulating steroid hormones and the risk of prostate cancer.Cancer Epidem Biomarkers Prev2006; 15: 86–91.
59.
Committee on Sports Medicine and Fitness.Adolescents and anabolic steroids: a subject review. American Accademy of Pediatrics.Pediatrics1997; 99: 904–908.
60.
DawsonR.T.Drugs in sport – the role of the physician.J Endocrinol2001; 170: 55–61.
