Childhood body mass index and the risk of prostate cancer in adult men

Prostate cancer is the second most common cancer among men worldwide and it is most frequent in high-income countries (World Cancer Research Fund/American Institute for Cancer Research, 2007; Globocan, 2012). Despite affecting large numbers of men, the aetiology of the disease is poorly understood. Moreover, none of the well-established risk factors such as age, ethnicity or a family history of prostate cancer are modifiable. Other prostate cancer risk factors that have been identified include adult obesity and dietary components, each of which are potentially modifiable, as well as non-modifiable risk factors such as adult height, genetic polymorphisms and hormonal factors. The contributions of these factors to the aetiology of prostate cancer are, however, unclear (Gronberg, 2003; Hsing and Chokkalingam, 2006). Adult anthropometry has been evaluated in relation to prostate cancer risk in several studies. Two meta-analyses have established that taller men have an increased risk of prostate cancer, however the effect sizes are modest (MacInnis and English, 2006;Zuccolo et al, 2008). Recently we found that tall boys, especially in late childhood, had an elevated risk of developing prostate cancer in adulthood (Cook et al, 2013). Additionally, several studies have found indications that adult obesity increases the risk of prostate cancer. However, the effect of greater adult body mass index (BMI; kg m−2) on prostate cancer risk is relatively weak (ranging in magnitude from a 3 to 6% increased risk per 5 kg m−2; MacInnis and English, 2006; Renehan et al, 2008), although the effects appear to be stronger for aggressive and fatal prostate cancers (MacInnis and English, 2006;Discacciati et al, 2011; Discacciati et al, 2012). As the growth of the prostate organ starts early in life, and the development of prostate cancer likely occurs over a long period before it manifests clinically, it is plausible that this process originates early in life (Freedland and Platz, 2007; Wilson, 2011). Consequently, childhood may represent an essential period where early exposures could affect prostate cancer risk later in life. Excess weight during childhood has various adverse consequences for long-term health (Ahlgren et al, 2004; Baker et al, 2007; Reilly and Kelly, 2011). Only a few studies have, however, investigated if childhood body size is associated with the risk of prostate cancer in adulthood, and their findings are equivocal (Andersson et al, 1995; Ilic et al, 1996; Giovannucci et al, 1997; Hsing et al, 2000; Dal et al, 2004; Jeffreys et al, 2004; Robinson et al, 2005; Barba et al, 2008). The only cohort study using measured heights and weights did not find an effect of childhood BMI, but this study was limited by a low number of prostate cancer cases as well as a wide age range of the included boys (Jeffreys et al, 2004). The remaining studies relied on a mid-life recall of childhood weight (Andersson et al, 1995; Ilic et al, 1996) or body size (Giovannucci et al, 1997; Hsing et al, 2000; Dal et al, 2004; Robinson et al, 2005; Barba et al, 2008), which might have resulted in exposure misclassification bias that usually results in attenuation of effects towards the null. We investigated whether a larger BMI in childhood, independent of and adjusted for height, as well as longitudinal changes in BMI during childhood were associated with an increased risk of prostate cancer in adulthood in a large Danish population-based cohort of men. In addition, to examine whether changes in diagnostic procedures over time and the stage of the cancer affected these associations, we conducted additional analyses exploring the effects of the introduction of prostate-specific antigen (PSA) testing and the Tumour, Node, Metastasis (TNM) stage of the neoplasm.