Prostate Cancer in Special Populations

Risk factors for prostate cancer have been discussed in detail in a previous chapter by Graham Giles (Chapter 1). As noted by Giles, in addition to the important effect of family history, it is notable that the incidence of prostate cancer varies substantially by ethnicity and nationality. This chapter explores these two factors in more detail, and focuses on special populations in which prostate cancer genetics has been explored in some detail including Icelanders, Poles, Ashkenazi Jews and African-Americans. Icelanders are an example of a geographical isolate. The population of Iceland is approximately 300,000 individuals, and immigration is uncommon. In addition, there have been several important sudden declines in population, the most notable of which was the arrival of smallpox in 1707 which killed more than one quarter of Iceland’s inhabitants. As a consequence of Iceland’s isolation, genetic heterogeneity may be less pronounced in Iceland compared to other European countries. As discussed by Julius Gudmundsson and Kári Stefánsson, several important low to moderate penetrance prostate cancer alleles were first discovered in this population, and these findings have been subsequently confirmed in many other populations. Founder effects in several disease genes have been demonstrated in Iceland. Perhaps the most well-known cancer-associated mutation is the 999del5 mutation in BRCA2, which is associated with a substantially increased risk for breast cancer and accounts for the vast majority of hereditary breast cancer cases in Iceland. Importantly, as discussed in the chapter by Eeles and colleagues (Chapter 8), this mutation has been shown to be associated with aggressive prostate cancer. The presence of a founder mutation enabled these studies to be conducted, as systematically identifying all BRCA2-postive prostate cancer cases at low cost in an outbred population is not technically feasible at the current time.