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Differential Gene Expression in Prostate Tissue According to Ejaculation Frequency.

ABSTRACT: In a prospective study of 31 925 men with 18 yr of follow-up, higher ejaculation frequency (EF) throughout adulthood was associated with lower rates of prostate cancer. To further explore this association, we evaluated whole transcriptome gene expression in the prostate tissue from study participants who developed prostate cancer between 1992 and 2004 (n=157 tumor tissue, n=85 adjacent normal). We tested for trends in gene expression according to the level of EF as self-reported in 1992 for ages 20-29 yr, 40-49 yr, and the year prior to the questionnaire, 1991. There were no associations between EF and gene expression in areas of tumor after accounting for multiple testing. In contrast, in the adjacent normal tissue, 409 genes and six pathways were differentially expressed at a false discovery rate ?0.2 across categories of EF in 1991. These results suggest that ejaculation affects the expression of genes in the normal prostate tissue. The identified genes and pathways provide potential biological links between EF and prostate tumorigenesis. PATIENT SUMMARY:To explore previous findings that men who ejaculate more frequently have lower risk of prostate cancer, we evaluated molecular alterations in the prostate tissue according to each man's frequency of ejaculation prior to diagnosis. We identified biological processes that could link ejaculation frequency and prostate cancer.

SUBMITTER: Sinnott JA

PROVIDER: S-EPMC6489461 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Differential Gene Expression in Prostate Tissue According to Ejaculation Frequency.

Sinnott Jennifer A JA Brumberg Katherine K Wilson Kathryn M KM Ebot Ericka M EM Giovannucci Edward L EL Mucci Lorelei A LA Rider Jennifer R JR

European urology 20180518 5

In a prospective study of 31 925 men with 18 yr of follow-up, higher ejaculation frequency (EF) throughout adulthood was associated with lower rates of prostate cancer. To further explore this association, we evaluated whole transcriptome gene expression in the prostate tissue from study participants who developed prostate cancer between 1992 and 2004 (n=157 tumor tissue, n=85 adjacent normal). We tested for trends in gene expression according to the level of EF as self-reported in 1992 for ages ...[more]

PMID: 29784192

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Project description:Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.To incorporate an additional 10 yr of follow-up into an original analysis and to comprehensively evaluate the association between ejaculation frequency and PCa, accounting for screening, clinically relevant disease subgroups, and the impact of mortality from other causes.A prospective cohort study of participants in the Health Professionals Follow-up Study utilizing self-reported data on average monthly ejaculation frequency. The study includes 31925 men who answered questions on ejaculation frequency on a 1992 questionnaire and followed through to 2010. The average monthly ejaculation frequency was assessed at three time points: age 20-29 yr, age 40-49 yr, and the year before questionnaire distribution.Incidence of total PCa and clinically relevant disease subgroups. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).During 480831 person-years, 3839 men were diagnosed with PCa. Ejaculation frequency at age 40-49 yr was positively associated with age-standardized body mass index, physical activity, divorce, history of sexually transmitted infections, and consumption of total calories and alcohol. Prostate-specific antigen (PSA) test utilization by 2008, number of PSA tests, and frequency of prostate biopsy were similar across frequency categories. In multivariable analyses, the hazard ratio for PCa incidence for ?21 compared to 4-7 ejaculations per month was 0.81 (95% confidence interval [CI] 0.72-0.92; p<0.0001 for trend) for frequency at age 20-29 yr and 0.78 (95% CI 0.69-0.89; p<0.0001 for trend) for frequency at age 40-49 yr. Associations were driven by low-risk disease, were similar when restricted to a PSA-screened cohort, and were unlikely to be explained by competing causes of death.These findings provide additional evidence of a beneficial role of more frequent ejaculation throughout adult life in the etiology of PCa, particularly for low-risk disease.We evaluated whether ejaculation frequency throughout adulthood is related to prostate cancer risk in a large US-based study. We found that men reporting higher compared to lower ejaculatory frequency in adulthood were less likely to be subsequently diagnosed with prostate cancer.

Project description:BackgroundTypical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies.MethodsTo examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors.ResultsStatistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.ConclusionsThe up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

Dataset Information

Differential Gene Expression in Prostate Tissue According to Ejaculation Frequency.

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Differential Gene Expression in Prostate Tissue According to Ejaculation Frequency.

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