The role of lifestyle characteristics on prostate cancer progression in two active surveillance cohorts.

Background Although much research has examined the relationship between lifestyle and prostate cancer (PCa) risk, few studies focus on the relationship between lifestyle and PCa progression. The present study examines this relationship among men initially diagnosed with low- to intermediate-risk PCa and managed with active surveillance (AS).Methods Men enrolled in two separate AS programs were recruited for this study. Data regarding clinical, demographic and lifestyle characteristics were collected. Results were then compared between men whose disease remained low- to intermediate-risk and men whose disease progressed.Results Demographic, clinical and physical characteristics were similar between comparative groups and cohorts, with the exception that age at the time of diagnosis and questionnaire was increased among men whose disease progressed. Lifestyle scores among men who remained low- to intermediate-risk were higher than those whose risk progressed; however, scores were only significant in one cohort on univariable analysis. On multivariable analysis, the only predictor of progression was age at diagnosis. Physical activity was consistently higher in both low risk groups, although this difference was insignificant. Consistent differences in other lifestyle variables were not observed.Conclusions Age remains an important predictor of PCa progression. Improving lifestyle characteristics among men initially managed with AS might help to reduce the risk of progression. Given the limitations of this study, more rigorous investigation is required to confirm whether lifestyle characteristics influence the progression of low- to intermediate-risk PCa

Duplication and Retention Biases of Essential and Non-Essential Genes Revealed by Systematic Knockdown Analyses

When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicableclose9