Molecular epidemiology of prostate cancer: hormone-related genetic loci

Abstract

Prostate cancer is the most common non-skin cancer and the second leading cause of cancer deaths among men in most Western countries. Despite its high morbidity and mortality, the etiology of prostate cancer remains obscure. Although compelling laboratory data suggest a role for androgens in prostate carcinogenesis, most epidemiologic data, including serological and genetic studies, are inconclusive. In this chapter, we review the status of serologic studies and discuss the importance of intra-prostatic hormone levels in possibly clarifying the often-contradictory data on serologic studies. To provide insights and directions for epidemiologic research on hormones and prostate cancer, this review centers on the molecular epidemiology of hormone-related genetic loci. These loci have been investigated in a number of studies to date and will undoubtedly expand even further as rich new genetic information sources and high-throughput genotyping and analysis methods become available. Due to the enormous number of these loci, we recommend careful analysis and cautious interpretation of studies of genetic markers, including microsatellites and single nucleotide polymorphisms (SNPs), as false positive and negative results are likely due to limited statistical power, multiple hypothesis testing, population stratification, or non-representative population sampling. This review also highlights the need for replication in various populations, as well as reasons for performing functional analyses of SNPs, a critical and often under-appreciated component of molecular epidemiologic investigations. The time is ripe for concerted, large-scale multidisciplinary investigations that incorporate molecular genetics, biochemistry, histopathology, and endocrinology into traditional epidemiologic studies. Such collaboration will lead to a deeper understanding of the etiologic pathways of prostate cancer, ultimately yielding better preventive, diagnostic, and therapeutic strategies.