Genetic Epidemiology of Prostate Cancer

摘要

Prostate cancer results from complex interactions among genetic, endocrine, and environmental factors. Understanding genetic risk factors that contribute to the occurrence of prostate cancer is crucial to design both preventative and therapeutic strategies and to identify at-risk individuals. Plausible candidates for susceptibility genes for prostate cancer risk include genes involved in insulin-like growth factor signaling, androgen signaling, and in immune response. We hypothesized that genetic variation in genes in these pathways was associated with prostate cancer risk. We studied 199 incident prostate cancer cases and 263 age-matched controls. Genotyping was performed for 59 polymorphisms in 18 genes and statistical analyses performed to look at their associations with prostate cancer risk and aggressiveness. As previously reported, the IRS1 G972R GR/RR genotypes (rs1801278) were associated with a significant 2.7-fold increased risk for prostate cancer (95% CI 1.5-4.9, p=0.0007). Other significant results were SNP rs2139924 in IGF1R with a 2.6- fold increased risk (95% CI 1.1-6.5) and rs361072 in PI3KCB with a 1.6 fold increased risk (95% CI 1.03-1.66). These results support a role of the insulin- like growth factor pathway in the etiology of prostate cancer. These results need to be replicated in multiple, larger studies.