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

  1. #21
    [#16]
    A Meta-Synthesis of Qualitative Studies Exploring Men’s Sense of Masculinity Post–Prostate Cancer Treatment
    [2017]

    https://journals.lww.com/cancernursingonline/Abstract/publishahead/A_Meta_Synthesis_of_Qualitative_Studies_Exploring. 99229.aspx

    Abstract

    Background: There has been little psychosocial research concerning men’s adaption to prostate cancer and treatment-related sexual dysfunction. Qualitative studies have explored men’s sense of self after treatment, but the data have yet to be synthesized.

    Objective: The aim of this study was to report a meta-synthesis of qualitative studies exploring men’s sense of masculinity after treatment of prostate cancer.

    Methods: Six databases were searched to identify relevant studies conducted and published between January 1990 and August 2016. Titles and abstracts were reviewed by 2 reviewers. Studies that met the inclusion criteria were selected and reviewed for quality. The extracted data were then synthesized.

    Results: A total of 14 studies met the inclusion criteria and passed the quality assessment. The meta-synthesis found that men’s sense of masculinity diminished after treatment of prostate cancer. Impotence, incontinence, and physical changes caused psychological stress. Underpinning these factors were cultural influences and dominant ideals of what it means to be a man.

    Conclusions: Men had entrenched ideas about what manhood entailed. The review found that men’s sense of masculinity was diminished posttreatment of prostate cancer. They felt that they could not exercise their manliness because of the adverse effects associated with prostate cancer treatment.

    Implications for Practice: More support and communication throughout the process are required to better inform patients of the outcomes of treatment. In addition, it would be beneficial to have open forums through which to encourage men to talk frankly about their masculine identities.
    [Emphasis mine]

  2. #22
    [#17]
    Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference
    [2017, Full Text]

    http://ascopubs.org/doi/10.1200/JCO.2017.74.1173

    Abstract

    Purpose
    Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management.

    Methods
    An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review.

    Results
    Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy.

    Conclusion
    To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA—a clinically heterogeneous disease.
    [Emphasis mine]

    Related news articles:
    Recommendations for genetic counseling, genetic testing for hereditary prostate cancer [2017]

    https://www.sciencedaily.com/releases/2017/12/171213161119.htm

  3. #23
    [#18]
    Concordance of Non–Low-Risk Disease Among Pairs of Brothers With Prostate Cancer
    [2018]

    https://www.ncbi.nlm.nih.gov/pubmed/29652556

    Abstract

    Purpose
    Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non–low-risk prostate cancer among brothers is affected by their genetic relation.

    Methods
    We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score ≤ 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen ≤ 10 ng/mL) or non–low risk. The odds ratio (OR) for concordance of non–low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)

    Results
    Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non–low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.

    Conclusion
    Non–low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non–low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

  4. #24
    [#19]
    Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries
    [2017, Full Text]

    https://www.nature.com/articles/ejcn2016162

    Abstract

    Background/Objectives:
    The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries.

    Subjects/Methods:
    A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6–13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=352. Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method.

    Results:
    There were no strong associations between prostate cancer risk and 37 dietary factors.

    Conclusions:
    Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.
    [Emphasis mine]

  5. #25
    [#20]
    Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial
    (SELECT) [2011, Full Text]

    https://jamanetwork.com/journals/jama/fullarticle/1104493

    Abstract
    Context The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.

    Objective To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.

    Design, Setting, and Participants A total of 35 533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34 887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.

    Interventions Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.

    Main Outcome Measures Prostate cancer incidence.

    Results This report includes 54 464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008 ); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18 ), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.

    Conclusion Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.

  6. #26
    [#21]
    Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project
    [2017]

    https://www.nature.com/articles/pcan201639

    Abstract

    Background:
    Epidemiologic and laboratory evidence supports a role for cholesterol in prostate cancer (PC). Dietary saturated fat content impacts serum cholesterol levels. However, epidemiologic associations between saturated fat and PC aggressiveness are inconsistent. We hypothesized that high saturated fat intake would be associated with increased PC aggressiveness, and that statin use would modify this association.

    Methods:
    Of 1854 PC cases in the North Carolina-Louisiana PC Project, 321 (17%) were classified as high aggressive (Gleason sum 8, PSA>20 ng ml−1, or Gleason sum 7 and clinical stage T3-4) or low/intermediate aggressive (all other cases). Using low/intermediate aggressive cases as the referent group, we examined the association between tertiles of total fat-adjusted saturated fat intake and high aggressive PC using logistic regression, overall and stratified by race and statin use. We examined total fat-adjusted polyunsaturated and monounsaturated fatty acids (PUFA and MUFA, respectively), trans fat and cholesterol intake in secondary analysis.

    Results:
    High total fat-adjusted saturated fat intake was associated with an elevated odds ratio (OR) for aggressive PC (ORT3vsT1 1.51; 95% CI 1.10–2.06; P-trend=0.009), with an attenuated association in statin users (ORT3vsT1 1.16; 95% CI 0.67–2.01; P-trend=0.661) compared with non-users (ORT3vsT1 1.71; 95% CI 1.16–2.51; P-trend=0.053). High total fat-adjusted cholesterol intake was associated with aggressive PC in European Americans (ORT3vsT1 1.62; 95% CI 1.02–2.58; P-trend=0.056), but not African Americans (ORT3vsT1 0.92; 95% CI 0.60–1.42; P-trend=0.750). High total fat-adjusted PUFA was inversely associated with PC aggressiveness (ORT3vsT1 0.75; 95% CI 0.55–1.03), although this was not significant. No associations were found between total fat-adjusted MUFA or trans fat and PC aggressiveness.

    Conclusions:
    High total fat-adjusted saturated fat intake was associated with increased PC aggressiveness, with a suggestion of a stronger effect in men not using statins. The association between total fat-adjusted cholesterol intake and PC aggressiveness was most pronounced in European Americans.
    [Emphasis mine]

  7. #27
    [#22]
    Nutrition, physical activity, and lifestyle factors in prostate cancer prevention
    [2018]

    https://journals.lww.com/co-urology/Abstract/2018/01000/Nutrition,_physical_activity,_and_lifestyle.10.asp x

    Abstract

    Purpose of review To review current evidence for prostate cancer prevention with nutrition, physical activity, and lifestyle interventions and identify future research directions.

    Recent findings Multiple preclinical and observational studies have observed that diet, exercise, and lifestyle interventions may play a role in mitigating disease progression, mortality, and overall disease burden for high-grade and fatal prostate cancer. Increased vegetable and fruit intakes, decreased red meat and saturated fat intakes, and increased exercise are potentially associated with decreased risk of incident disease and increased progression-free, prostate cancer-specific, and overall survival. Randomized controlled trials (RCTs) have demonstrated that selenium and vitamin C supplements are ineffective in preventing incident prostate cancer and that vitamin E supplements potentially increase incident prostate cancer risk. A large RCT of a high vegetable diet intervention among prostate cancer patients on active surveillance, the Men's Eating and Living study, will soon complete analysis. An RCT for an exercise intervention among men with metastatic castrate-resistant prostate cancer is currently accruing.

    Summary Although preclinical and observational studies have identified potential benefits for high vegetable, low fat, low meat diets, and increased exercise, Level I evidence is limited. To inform clinical care, future research should focus on RCTs evaluating clinical effectiveness.
    [Emphasis mine]

  8. #28
    [#23]
    MOLECULAR CLASSIFIER TESTING FOR NEWLY DIAGNOSED LOCALIZED PROSTATE CANCER IN THE STATE OF MICHIGAN
    [2018, Full Text]

    https://www.sciencedirect.com/science/article/pii/S0022534718419520

    INTRODUCTION AND OBJECTIVES
    Tissue-based molecular classifier (MC) tests may assist with management decisions in patients with newly diagnosed prostate cancer (PCa). While retrospective data has supported the validity, there is little published data regarding their real-world use. We sought to determine and compare the current patterns of use of the Decipher Biopsy, Oncotype DX, and Prolaris tests across a diverse, statewide quality improvement collaborative.

    METHODS
    We analyzed all patients with newly diagnosed PCa who underwent prostate biopsy at one of 44 MUSIC practices, which includes >90% of urology practices in Michigan. We prospectively collected data on the use of three tissue-based MC tests: Decipher Biopsy, Oncotype DX Prostate, and Prolaris. We determined associations between MC use and demographic and clinical data, including age, race, Charlson Comorbidity Index (CCI), Gleason score, and clinical T (cT) stage, as well as variation across practices. Similar analyses were performed in the ″AS-appropriate″ subgroup: those considered candidates for Active Surveillance (AS) based on MUSIC AS Appropriateness Criteria (Gleason 3+3 and low volume Gleason 3+4).

    RESULTS
    A total of 3,968 men were diagnosed with clinically localized PCa from Jan-Sept 2017, and 727 (18.3%) underwent MC testing with Decipher (n=236), Oncotype DX (n=67), and Prolaris (n=424). 317/727 (43%) of tests were performed on AS-appropriate patients. MC testing was associated with biopsy Gleason grade of 7, lower cT stage, lower prostate specific antigen, and a greater number of CCI (all p<0.05). In the AS-appropriate subgroup, MC testing was associated with a Gleason score of 3+4 (vs 3+3), African American race, increasing CCI, and lower cT stage (p<0.05). Variability of MC testing among practices ranged from 0% to 93%, with 6 practices performing MC testing on ≥60% and 29 practices performing MC testing on <5% of newly diagnosed patients. In AS-appropriate patients, 111 (35.5%) had MC test results above the test-specific AS threshold. Conversely, of 113 patients with low volume Gleason 3+4 disease, 50 (44.2%) had MC test results below the AS threshold.

    CONCLUSIONS
    There is variability of MC testing in patients with newly diagnosed localized PCa, and testing is performed in both AS-appropriate and higher risk patients. In AS-appropriate patients, there is greater use of testing in Gleason 3+4 patients, and nearly half of these patients have results supporting potential eligibility for AS. Additional follow-up will help determine whether MC tests may assist with clinical management.
    [Emphasis mine]

  9. #29
    [#24]
    A 24‐year prospective study of dietary α‐linolenic acid and lethal prostate cancer
    [2018]

    https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31247

    Abstract
    Several meta‐analyses have attempted to determine the relationships between intake of α‐linolenic acid (ALA) and prostate cancer, but results were inconclusive. 47,885 men aged 40–75 years without prior cancer in the Health Professionals Follow‐Up Study were prospectively followed from 1986 to 2010. Intake of ALA was determined from validated food frequency questionnaires every 4 years. We used multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for lethal prostate cancer (distant metastasis or prostate cancer death). 386 lethal prostate cancers were diagnosed in the pre‐PSA era (before February, 1994) and 403 cancers in the PSA era. Intake of ALA was associated with increased risk of lethal prostate cancer in the pre‐PSA era (comparing top to bottom quintile of intake, multivariate‐adjusted HR = 1.78; 95% CI = 1.22–2.06; ptrend = 0.003), but not in the PSA era (HR = 0.81; 95% CI = 0.56–1.17; ptrend = 0.53), and the difference in associations was statistically significant (p for interaction = 0.02). Mayonnaise, a primary food source of ALA intake in our cohort, was likewise only significantly associated with lethal prostate cancer in the pre‐PSA era. Among many other fatty acids that are correlated with ALA due to shared food sources, none was associated with lethal prostate cancer in the pre‐PSA era. In conclusion, higher intake of ALA was associated with an increased risk of lethal prostate cancer in the pre‐PSA era, but not in the PSA era. Potential reasons for the differential associations warrant further investigation.
    [Emphasis mine]

  10. #30
    [#25]
    The emerging role of obesity, diet and lipid metabolism in prostate cancer
    [2017, Full Text]

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619099/

    Abstract

    Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.
    EXECUTIVE SUMMARY

    • Evidence obtained in large case–control studies suggests that obesity is associated with an increased risk of being diagnosed with high-grade prostate cancer and dying of the disease.
    • The increased risk of high-grade prostate cancer in obese men has a strong biological rationale, which includes systemic effects, such as the increased levels of IGF-1 and decreased levels of testosterone, as well as increased levels of inflammation and cytokines, and also local effects, such as larger prostates and periprostatic fat accumulation.
    • As far as dietary habits are concerned, saturated fat may increase the risk of prostate cancer-related death, while vegetable fat may exert a protective effect after a diagnosis of nonmetastatic prostate cancer.
    • Unlike other malignancies, prostate cancer is highly dependent on lipid metabolism, with free fatty acids being able to support cell growth, proliferation, differentiation and motility via binding to several biological targets, such as the nuclear PPAR-γ.
    • Prostate cancer cells present both intratumoral lipogenesis and steroidogenesis, which can provide druggable targets for prevention and treatment purposes.

 

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