Research Article Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study Zo€ e Hyde 1,2 , Leon Flicker 1,2 , Kieran A. McCaul 1,2 , Osvaldo P. Almeida 1,3,4 , Graeme J. Hankey 2,5 , S. A. Paul Chubb 2,6 , and Bu B. Yeap 2,7 Abstract Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer. Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010. Results: During a mean follow-up period of 6.7  1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00– 1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers. Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer. Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev; 21(8); 1319–29. Ó2012 AACR. Background Cancer is a leading cause of death and burden of disease (1). Lifestyle factors, such as smoking, poor diet, and physical inactivity account for a significant proportion of cases, but sex hormones are thought to have a role in the aetiology of some cancers. The prostate is an androgen-dependent organ; ade- quate levels of testosterone and its potent 5a-reductase (5AR) derived metabolite, dihydrotestosterone (DHT), are required for normal development, growth, and func- tion (2). Development is inhibited in 46, XY individuals with androgen insensitivity syndromes or 5AR deficien- cy, whereas androgen deprivation therapy leads to atro- phy of the prostate and other male reproductive tissues (3, 4). Males who undergo orchidectomy in adolescence or early adulthood rarely develop prostate cancer, whereas testosterone therapy can hasten progression of the dis- ease (2). Conversely, androgen deprivation therapy is an effective palliative treatment and remains the gold stan- dard (5). However, the relationship between endogenous testos- terone and incident prostate cancer remains controversial. Some prospective studies have reported that higher tes- tosterone levels are associated with increased risk (6, 7), although the majority have not found a statistically sig- nificant association (8, 9). However, many of the latter studies are underpowered and have failed to consider the problem of competing risks. The question of whether Authors' Affiliations: 1 Western Australian Centre for Health and Ageing, Centre for Medical Research, Western Australian Institute for Medical Research; Schools of 2 Medicine and Pharmacology and 3 Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley; Depart- ments of 4 Psychiatry and 5 Neurology, Royal Perth Hospital, Perth; 6 Path- West, Department of Biochemistry; 7 Department of Endocrinology and Diabetes, Fremantle Hospital, Fremantle, Western Australia, Australia Note: Supplementary data for this article are available at Cancer Epide- miology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). Corresponding Author: Zo€ e Hyde, WA Centre for Health and Ageing (M570), University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Phone: þ61-8-9224-2750; Fax: þ61-8-9224-8009; E-mail: zoe@sexologyresearch.org doi: 10.1158/1055-9965.EPI-12-0129 Ó2012 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention www.aacrjournals.org 1319 on May 22, 2020. © 2012 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from Published OnlineFirst July 24, 2012; DOI: 10.1158/1055-9965.EPI-12-0129