EARLY GROWTH, ADULT BODY SIZE AND PROSTATE CANCER RISK Graham G. GILES 1 * , Gianluca SEVERI 2 , Dallas R. ENGLISH 1,5 , Margaret R.E. MCCREDIE 3,4 , Robert MACINNIS 1 , Peter BOYLE 2 and John L. HOPPER 6 1 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia 2 Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy 3 Department of Preventive and Social Medicine, Dunedin Medical School, University of Otago, New Zealand 4 Cancer Epidemiology Research Unit, New South Wales Cancer Council, Woolloomooloo, New South Wales, Australia 5 Department of Public Health, University Western Australia, Perth, Western Australia, Australia 6 Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia The role of growth from birth through puberty and through adult life has been the subject of epidemiologic in- vestigation in regard to the risk of prostate cancer but the evidence remains weak and inconsistent. We investigated associations between prostate cancer risk and a number of markers of body growth, size and changes to size in a popu- lation-based, case-control study in Australia from 1994 to 1998. We analyzed data obtained in face-to-face interviews from 1,476 cases and 1,409 controls. The main outcomes of interest were the timing of the growth spurt in adolescence, the experience of acne and interviewer observation of facial acne scarring, body size at age 21, body size in reference year, maximum body weight and rate of body size change since age 21 years. Analysis was performed on all cases and also by tumour grade. We found no associations with mea- sures of body size including body mass index and lean body mass at age 21 or later in adult life. Having a growth spurt later than friends reduced risk (odds ratio [OR] 0.79 [0.63– 0.97]) and some measures of acne also gave odds ratios less than 1, for example, having facial acne scarring gave an OR of 0.67 (0.45–1.00). We conclude that markers of delayed an- drogen action, such as delayed growth spurt in puberty, and markers of other androgen-dependent activity in puberty, such as facial acne scarring, are associated with prostate cancer risk but we could detect no associations with markers of adult body size and growth including lean body mass. © 2002 Wiley-Liss, Inc. Key words: prostate cancer; anthropometry; growth Although prostate cancer (PCa) is a disease of older men, early physical growth and development might be important in influenc- ing PCa risks that will only be manifested many years later. 1 Measures of body mass in adult life might also be associated with PCa risk, but a recent review described the evidence relating various body dimensions such as height and body mass index (BMI) to PCa risk as weak and inconsistent. 2 One contributory factor to this inconsistency is the wide variation in quality of studies, particularly in regard to their statistical power—the liter- ature is replete with many small case-control studies that have also depended on self-reported estimates of body dimensions. 3 Another factor affecting consistency of findings is poor disease specificity, since most epidemiologic studies accept all PCa as one biologic entity when it is probable that PCa is biologically heterogeneous not only in terms of grade and stage but also with respect to its clinical behaviour. 4 The use of BMI as a measure of obesity also presents difficulties as BMI does not differentiate between lean mass and fat mass 2,5 but at certain ages may be more closely associated with lean mass, e.g., during adolescence. As lean body mass (LBM) is associated with androgen and other growth-factor activity 6,7 and fat mass (FM) is associated with increased oestro- genic activity, 8 these 2 elements of body mass are likely to have different associations with a hormone-dependent malignancy such as PCa. BMI also combines height and weight, each of which has separate determinants. We conducted a large case-control study of PCa to see if we could detect any associations with markers of early growth and adult body size, particularly with respect to relatively early age at onset (70 years of age) and tumours of moderate to high grade. We hypothesised, reasoning by analogy with menarche and breast cancer, that early andrarche would be positively associated with PCa risk and late andrarche with reduced risk; the former being related to high and the latter with low androgen activity. We also hypothesised that LBM would be positively associated with PCa risk because of the known dependency of both LBM and PCa on androgens and other growth factors. 6,7 Similarly, we hypothesised that FM would be negatively associated with PCa risk because of the likely increased production of oestrogens by peripheral aroma- tisation in adipose tissue 8 and a possible protective effect of a consequently increased ratio of oestrogens to androgens. 9 MATERIAL AND METHODS We carried out a population-based, case-control study of PCa in Melbourne, Sydney and Perth, Australia, details of which have been published before. 10 Subjects were usual residents of the 3 cities’ metropolitan areas. The study protocol was approved by all relevant human research ethics committees in Victoria, New South Wales and Western Australia. Eligible cases comprised all male residents of Melbourne, Sydney and Perth diagnosed from 1994 to 1997 and notified to the population-based cancer registries with a histopathology-confirmed diagnosis of adenocarcinoma of the prostate (International Classification of Diseases 9th revision ru- bric 185), excluding well-differentiated tumours (defined as low grade, i.e., those with Gleason scores 5). Cases had to be aged 70 years at diagnosis and registered on the State Electoral Rolls (adult registration to vote is compulsory in Australia). All cases diagnosed before the age of 60 years were included. Initially, random samples of 50% of cases diagnosed aged 60 – 64 and 25% of cases diagnosed aged 65– 69 were selected, with the proportions varying over time to fit interview quotas. Controls were randomly selected from men on the current State Electoral Rolls and were frequency matched to the age distribution of the cases in a ratio of 1 control per case. Potential controls were matched against the cancer registries at the time of recruitment to exclude men with a known history of PCa. Three controls were Grant sponsor: National Health and Medical Research Council; Grant number: 940394; Grant sponsor: Tattersall’s; Grant sponsor: The Whitten Foundation; Grant sponsor: The Cancer Council Victoria. *Correspondence to: Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton South, Australia 3053. Fax: +61-3-9635-5330. E-mail: Graham.Giles@cancervic.org.au Received 22 May 2002; Revised 17 June 2002; Accepted 25 August 2002 DOI 10.1002/ijc.10810 Int. J. Cancer: 103, 241–245 (2003) © 2002 Wiley-Liss, Inc. Publication of the International Union Against Cancer