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Thread: (E) Risk Population Studies Genomic & Genetic Testing

  1. #121
    [#109]
    Vasectomy and prostate cancer risk: a 38-year nationwide cohort study
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31119294

    Abstract

    BACKGROUND:
    A man's risk of prostate cancer has been linked to his prior reproductive history, with low sperm quality, low ejaculation frequency, and a low number of offspring being associated with increased prostate cancer risk. It is however highly controversial whether vasectomy, a common sterilization procedure for men, influences prostate cancer risk.

    METHODS:
    We established a cohort of all Danish men (born from 1937) and linked information on vasectomy, doctor visits, socioeconomic factors and cancer from nationwide registries using unique personal identification numbers. Incidence risk ratios for prostate cancer by time since vasectomy and age at vasectomy during the follow-up were estimated using log-linear Poisson regression.

    RESULTS:
    Overall, 26,238 cases of prostate cancer occurred among 2,150,162 Danish men during 53.4 million person-years of follow-up. Overall, vasectomized men had an increased risk of prostate cancer compared with non-vasectomized men (relative risk 1.15; 95% CI, 1.10 to 1.20). The increased risk of prostate cancer following vasectomy persisted for at least 30 years after the procedure and was observed regardless of age at vasectomy and cancer stage at diagnosis. Adjustment for the number of visits to doctor and socioeconomic factors did not explain the association.

    CONCLUSIONS:
    Vasectomy is associated with a statistically significant increased long-term risk of prostate cancer. The absolute increased risk following vasectomy is nevertheless small, but our finding supports a relationship between reproductive factors and prostate cancer risk.

    Is vasectomy a cause of prostate cancer? [2019, Editorial]

    ...An important consideration is the ultimate public health impact of a causal association. 500,000 U.S. men undergo vasectomy annually. Given the possible effect
    size, the absolute number of men at risk of lethal prostate cancer due to vasectomy is likely small. Its study, however, may shed light on mechanisms underlying cancer
    pathogenesis. A man's decision to undergo vasectomy should be decided based on the totality of evidence and consideration of benefits and possible risks.

  2. #122
    [#110]
    Who Dies From Prostate Cancer? An Analysis of the Surveillance, Epidemiology and End Results Database
    [2019]

    https://www.sciencedirect.com/scienc...36655519301918

    Highlights

    • Patients diagnosed with high-risk localised, node-positive or metastatic prostate cancer make up about 40% of this cohort.
    • The same three groups account for two-thirds of all deaths from prostate cancer.
    • Compared to low-risk localised disease, de novo metastatic disease carries a 40-fold greater risk of prostate cancer death.

    Abstract

    Aims
    To characterise the presenting features of those who ultimately die from prostate cancer (PCa).

    Materials and methods
    The study population consisted of patients in the Surveillance, Epidemiology and End Results (SEER) Program database diagnosed with PCa between 1990 and 2015. Patients were assigned to the following clinical risk groups: low-risk localised (LRL), intermediate-risk localised (IRL), high-risk localised (HRL), node-positive and metastatic (M1). Before 2004, in the absence of prostate-specific antigen (PSA) and Gleason score data, patients with cT1-T2aN0M0 and low-grade PCa were classified as LRL, those with cT3-4N0M0 or high-grade PCa were classified as HRL and all others with N0M0 disease were classified as IRL. The primary aim was to describe the risk group distribution of those who ultimately died from PCa compared with those who were diagnosed with PCa over the study period. A secondary aim was to estimate PCa-specific survival (PCSS) and evaluate the association of risk group with PCSS.

    Results
    Among a total of 811 487 patients who were diagnosed with PCa, data sufficient for risk group determination were present in 635 733 patients. The median follow-up was 83 months. The overall risk group distribution at diagnosis was as follows: LRL 10.5%, IRL 49.7%, HRL 34.8%, node-positive 1.5% and M1 3.5%. The risk group distribution of those who died from PCa was 3.9%, 29.4%, 40.9%, 3.2% and 22.8%, respectively. Compared with LRL PCa, the adjusted hazard ratio (95% confidence interval) for PCSS was 1.40 (1.33–1.46) in IRL, 3.76 (3.60–3.93) in HRL, 11.87 (11.14–12.65) in node-positive and 37.12 (35.43–38.88 ) in M1.

    Conclusions
    In this large contemporary cohort, patients with M1, node-positive and HRL disease accounted for two-thirds of all deaths from PCa. De novo metastatic PCa was associated with an approximately 40-fold increased risk of death from PCa compared with LRL PCa. Efforts to improve PCSS will therefore depend largely on improvements in therapy in those with M1, node-positive and HRL disease.

  3. #123
    [#111]
    Prostate Cancer Incidence and Mortality in Relationship to Family History of Prostate Cancer; Findings from The PLCO Trial
    [2019]

    https://www.clinical-genitourinary-c...153-3/fulltext

    ABSTRACT

    Objective
    To determine the relationship between family history of prostate cancer in a first-degree relative (FDR) and prostate cancer incidence and mortality.

    Methods
    De-identified datasets of men recruited in the Prostate, Lung, Colorectal, and Ovary (PLCO) trial were accessed. Men with complete information about family history of prostate cancer in an FDR were included. The impact of family history on prostate cancer incidence and mortality was assessed in a multivariate Cox regression model. Likewise, the impact of the number of FDRs with prostate cancer and the impact of youngest diagnosis age of an FDR with prostate cancer were assessed.

    Results
    A total of 74781 participants were included in the current analysis; including 5281 participants with family history of prostate cancer in an FDR and 69500 participants without family history of prostate cancer in an FDR. Among participants without family history of prostate cancer in an FDR, a total of 7450 patients (10.5%) were subsequently diagnosed with prostate cancer; while among patients with family history of prostate cancer in an FDR, a total of 889 patients (16.5%) were subsequently diagnosed with prostate cancer. In an adjusted multivariate Cox regression model, family history of prostate cancer was associated with a higher probability of prostate cancer diagnosis (HR: 1.590; 95% CI: 1.482-1.705; P<0.001). The number of FDRs with prostate cancer proportionally correlated with higher prostate cancer incidence (HR: 1.529; 95% CI: 1.439-1.624; P<0.001). Family history of prostate cancer in an FDR was not predictive of higher prostate cancer mortality in the PLCO screening (intervention) arm (HR: 0.829; 95% CI: 0.422-1.629; P= 0.587) while it was predictive of a higher prostate cancer mortality in the PLCO non-screening (control) arm (HR: 1.894; 95% CI: 1.154-3.109; P= 0.012). Number of FDRs with prostate cancer was not associated with higher prostate cancer mortality in the PLCO screening (intervention) arm (HR: 0.956; 95% CI: 0.541-1.691; P=0.878 ), while it was associated with higher prostate cancer mortality in the PLCO non-screening (control) arm (HR: 1.643; 95% CI: 1.083-2.493; P= 0.020).

    Conclusions
    Family history of prostate cancer is associated with an increased risk of prostate cancer diagnosis in the overall cohort of patients as well as a higher risk of prostate cancer mortality in the non-screened sub-cohort. Further prospective assessment of the role of screening among selected high-risk populations (including those with strong family history) is warranted.
    [Emphasis mine]

  4. #124
    [#112]
    Dairy Products: Is There an Impact on Promotion of Prostate Cancer? A Review of the Literature
    [2019, Full Text]

    https://www.frontiersin.org/articles...019.00062/fullhttps://www.frontiersin.org/articles...019.00062/full

    This review of the literature aims to study potential associations between high consumption of milk and/or dairy products and prostate cancer (PC). Literature is scarce, yet there is a direct relationship between mTORC1 activation and PC; several ingredients in milk/dairy products, when in high concentrations, increase signaling of the mTORC1 pathway. However, there are no studies showing an unequivocal relationship between milk products PC initiation and/or progression. Three different reviews were conducted with articles published in the last 5 years: (M1) PC and intake of dairy products, taking into account the possible mTORC1signaling mechanism; (M2) Intake of milk products and incidence/promotion of PC; (M3) mTORC1 activation signaling pathway, levels of IGF-1 and PC; (M4) mTORC pathway and dairy products. Of the 32 reviews identified, only 21 met the inclusion criteria and were analyzed. There is little scientific evidence that directly link the three factors: incidence/promotion of PC, intake of dairy products and PC, and PC and increased mTORC1 signaling. Persistent hyper-activation of mTORC1 is associated with PC promotion. The activity of exosomal mRNA in cellular communication may lead to different impacts of different types of milk and whether or not mammalian milks will have their own characteristics within each species. Based on this review of the literature, it is possible to establish a relationship between the consumption of milk products and the progression of PC; we also found a possible association with PC initiation, hence it is likely that the intake of dairy products should be reduced or minimized in mens' diet.
    [Emphasis mine]

  5. #125
    [#113]
    Relative risks of prostate cancer associated with different family cancer histories
    [2019]

    https://ascopubs.org/doi/abs/10.1200....15_suppl.1505

    Abstract

    Background: Recently developed clinical guidelines have suggested that men in families with Hereditary Prostate Cancer (HPC), Hereditary Breast and Ovarian Cancer (HBOC), and Lynch Syndrome (LS) be referred for consideration of genetic testing, especially in the setting of aggressive disease. However, while a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of risk associated with specific FH, and particularly with respect to known familial cancer syndromes, in a single population is needed. Methods: The Utah Population Database was used to identify 569,320 men, 40+ years with a pedigree that included at least three consecutive generations. Each man was evaluated for FH of FPC, HPC, HBOC and LS, as well as their own PC status. PC cases (N=34,889) were identified from both the SEER Utah Cancer Registry and death certificates and classified into one or more subtypes: early-onset (EO [age of diagnosis <60 years]), lethal, and/or aggressive (Gleason Grade ≥7, metastatic, or lethal). Relative risks (RR) associated with each PC subtype, adjusted for important covariates, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding confidence intervals (CIs) for each FH definition. Results: A FH of HPC conveyed the greatest relative risk for all PC subtypes (RR=2.30; 95% CI 2.21-2.39), followed by HBOC and LS. Furthermore, the strongest risks associated with FH were generally observed for EO disease. No differences in risk by degree of FH were observed for either lethal or aggressive disease. Conclusions: In this large population-based family database, the risk of PC was shown to vary by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.

  6. #126
    [#114]
    Incidence of second primary neoplasms among cancer survivors in the United States, 2000 through 2015
    [2019]

    https://ascopubs.org/doi/abs/10.1200....15_suppl.1586

    Background: The number of cancer survivors in the United States is projected to exceed 20 million by 2024. Survivors are at risk of developing a second primary neoplasm (SPN) – a leading cause of survivor death. We described the risk of developing a SPN among survivors of common cancers (smoking-related vs non-smoking-related) in the United States. Methods: We identified patients aged ≥18 years who were diagnosed with a primary cancer from the 10 sites with highest survival rates and stratified as smoking-related (urinary bladder, kidney & renal pelvis, uterine cervix, oral cavity & pharynx, and colon & rectum) and non-smoking related (prostate, thyroid, breast, corpus & uterus, and non-Hodgkin lymphoma) from Surveillance, Epidemiology, and End Results (2000-2015). SPN was defined as the first subsequent primary cancer occurring ≥2 months after first cancer diagnosis. Excess SPN risk was quantified using standardized incidence ratios (SIRs) stratified by sex. Results: A cohort of 2,908,349 patients (50.1% female) was identified and 260,267 (9.0%) developed SPN (7.6% of females and 10.3% of males). All index cancer sites were associated with a significant increase in SPN risk for females and males (except prostate cancer). Index smoking-related cancers (SIR range 1.20 – 2.17 for females and 1.12 – 1.91 for males) had higher increased risk of SPN than non-smoking-related cancers (SIR range 1.08 – 1.39 for females and 0.55 – 1.38 for males) relative to the general population. Conclusions: Nearly 10% of cancer survivors developed an SPN, and those with smoking-related cancers had higher risk. Given the increasing number of cancer survivors and importance of SPN as a cause of cancer death, these findings can improve secondary prevention and surveillance guidelines.
    It would have been helpful if there was a breakdown by primary treatment, RT vs RP.

  7. #127
    [#115]
    Screening, Active Surveillance, and Treatment of Localized Prostate Cancer Among Carriers of Germline BRCA Mutations
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31147265

    Abstract

    Male carriers of BRCA mutations are at higher risk of developing prostate cancer. Many issues are still unanswered and are currently being studied, including differences between BRCA1 and BRCA2, screening and specific protocols, the role of active surveillance, and the choice of definitive treatment

  8. #128
    [#116]
    Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men with Late-Onset Hypogonadism
    [2019]

    https://www.ncbi.nlm.nih.gov/pubmed/31145457

    Abstract

    The association between the use of testosterone replacement therapy (TRT) and prostate cancer remains uncertain. Thus, we investigated whether TRT is associated with an increased risk of prostate cancer in men with late-onset hypogonadism. We used the United Kingdom Clinical Practice Research Datalink to assemble a cohort of 12,779 men newly-diagnosed with hypogonadism between 1 January 1995 and 31 August 2016, with follow-up until 31 August 2017. Exposure to TRT was treated as a time-varying variable and lagged by 1 year to account for cancer latency, with non-use as the reference category. During 58,224 person-years of follow-up, a total of 215 patients were newly-diagnosed with prostate cancer, generating an incidence rate of 3.7 per 1,000 person-years. In time-dependent Cox proportional hazards models, use of TRT was not associated with an overall increased risk of prostate cancer (hazard ratio = 0.97; 95% confidence interval: 0.71, 1.32), compared with non-use. Results remained consistent in secondary and sensitivity analyses, as well as in a propensity score-matched cohort analysis that further assessed the impact of residual confounding. Overall, the use of TRT was not associated with an increased risk of prostate cancer in men with late-onset hypogonadism.

  9. #129
    [#117]
    Presentation and Outcomes of First-Degree Relatives Treated with Brachytherapy for Clinically Localized Prostate Cancer [2019]


    https://ideas.repec.org/a/abr/oajuns...8i2p33-37.html

    Abstract

    Purpose- To determine if first-degree relatives treated with definitive radiation for clinically localized prostate cancers have similar baseline characteristics and clinical outcomes. Methods- From a prospectively assembled database, we identified a set of first-degree relatives with clinically localized prostate adenocarcinoma. Patients were treated with brachytherapy with or without external beam radiation therapy. Biochemical failure was the primary outcome. Toxicities were measured with the International Prostate Symptom Score (IPSS) and Mount Sinai Erectile Function Score (MSEF). Results - We identified 41 patients including 22 pairs of first-degree relatives. One family included 3 separately treated brothers. The median follow up was 72 months. Eight pairs of first-degree relatives presented with the same Gleason score, representing 36% of pairs. Eleven pairs of relatives (50%) fell in the same NCCN risk category. There were 4 total biochemical failures, representing 9.8% of the cohort. In a single pair of brothers both patients experienced a biochemical failure. Therefore, in two pairs of relatives (9.1%) a different biochemical outcome was experienced. In the pair of brothers who both experienced biochemical failure, both brothers developed metastatic disease. One of the brothers died due to prostate cancer. Amongst pairs of first-degree relatives, 10 pairs (52%) experienced a concordant change in IPSS relative to the average. Fifty percent of pairs experienced concordant changes in MSEF score.

  10. #130
    [#118]
    Dairy Product Consumption and Prostate Cancer Risk in the US (P05-034-19)
    [2019]

    https://academic.oup.com/cdn/article...034-19/5517945

    Abstract

    Objectives
    We prospectively investigated the association between dairy product intake and prostate cancer risk among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort.

    Methods
    Pre-diagnostic dairy product intake was assessed using a validated food frequency questionnaire. Incident prostate cancer was ascertained by study visits, local cancer registries, or self-reports and only pathologically-verified cases were included in the analysis. In addition to overall prostate cancer, we classified cases by severity (early vs late stage, or low vs high Gleason scores). Using multivariate Cox regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of prostate cancer risk with dairy product intake, as total (all dairy products), by fat content (low- or high-fat), or by fermentation methods (fermented or non-fermented).

    Results
    Among 49,472 men, 4134 were diagnosed with prostate cancer during an average follow-up period of 11.2 years. The median total dairy product intake was 101 g/1000 Kcal. Total dairy product consumption was not statistically significantly associated with risk of any prostate cancer or stratified by disease severity. The HR (95% CI) comparing the highest with the lowest quartiles of total dairy product intake was 1.05 (0.96–1.15) for overall prostate cancer risk and ranged from 1.00 (0.88–1.14), for risk of prostate cancer with high-Gleason score, to 1.24 (0.93–1.66), for risk of late-stage prostate cancer. The only statistically significant finding in our stratified analyses was a positive association between high-fat dairy product intake and late-stage prostate cancer risk (HR = 1.37, 95% CI = 1.04–1.82, P-trend = 0.02). However, associations with high-fat dairy intake did not differ by stage (P = 0.15), suggesting a chance finding for the positive association with late-stage prostate cancer.

    Conclusions
    These preliminary findings do not support the previously-reported harmful impact of dairy product consumption on prostate cancer risk among US men. The observed association of high-fat dairy intake with late-stage prostate cancer needs to be confirmed in other studies.

 

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