Molecular epidemiology of prostate cancer: hormone-related genetic loci

Division of Epidemiology, School of Public Health, University of California, Berkeley, CA 94707, USA.
Frontiers in Bioscience (Impact Factor: 3.52). 02/2007; 12(9):3436-60. DOI: 10.2741/2325
Source: PubMed


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.

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    • "Although the prostate cancer rate is lower in China than that in Western countries, the incidence of prostate cancer has increased rapidly among Chinese men over the recent years [5] . As shown in previous studies, both genetic and environmental factors are involved in the development of prostate cancer [6] [7] [8] . "
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    ABSTRACT: Caspase-8 (CASP8) plays a key role in apoptosis. We examined by genotyping whether the -652 six-nucleotide insertion-deletion (6N ins/del) polymorphism in the CASP8 promoter region was associated with prostate cancer risk in a hospital-based case-control study of 406 Chinese prostate cancer patients and 408 age-matched cancer-free controls. Additionally, 23 prostate cancer tissues were analyzed for CASP8 mRNA expression. We found a significantly decreased prostate cancer risk for the 6N ins/del genotype [adjusted odds ratio (OR)=0.68; 95% confidence interval (CI)=0.51-0.92] and del/del genotype (OR=0.34; 95% CI=0.19-0.63) compared with the ins/ins genotype. The 6N del allele was associated dose-dependently with decreased prostate cancer risk (P trend = 0.001). RT-PCR showed that individuals with the 6N del allele had lower CASP8 mRNA levels than those with the ins/ins genotype (P = 0.024). These findings suggested that the CASP8-652 6N ins/del polymorphism may affect the susceptibility to prostate cancer and reduce prostate cancer risk among Chinese men.
    Full-text · Article · Mar 2011
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    • "It is thought that prostate cancer could result from a complex interplay between several environmental, lifestyle and genetic factors. (10–13) "
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    ABSTRACT: Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980's, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. Subjects were interviewed about their occupation histories, and a team of industrial hygienists assigned their past exposures using a checklist of some 300 chemicals. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. We created a pool of 183 controls combining the patients with cancers at sites other than the prostate and the population controls. We then estimated the odds ratio for prostate cancer associated with exposure to each of 10 agricultural chemicals, i.e., pesticides, arsenic compounds, acetic acid, gasoline engine emissions, diesel engine emissions, polycyclic aromatic hydrocarbons from petroleum, lubricating oils and greases, alkanes with >or=18 carbons, solvents, and mononuclear aromatic hydrocarbons. Based on a model adjusting for age, ethnicity, education, and respondent status, there was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides [odds ratio (OR)=2.3, 95% confidence interval (CI) 1.1-5.1], as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions (OR=5.7, 95% CI 1.2-26.5). The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need further confirmation in larger samples.
    Full-text · Article · Jan 2009 · McGill journal of medicine: MJM: an international forum for the advancement of medical sciences by students
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