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Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study.

ABSTRACT: Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population.This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40-70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.The proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives.ClinicalTrials.gov: NCT02053805.

SUBMITTER: Margel D

PROVIDER: S-EPMC4223504 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study.

Margel David D Benjaminov Ofer O Ozalvo Rachel R Shavit Grievink Liat L Kedar Inbal I Yerushalmi Rinat R Ben-Aharon Irit I Neiman Victoria V Yossepowitch Ofer O Kedar Daniel D Levy Zohar Z Shohat Mordechai M Brenner Baruch B Baniel Jack J Rosenbaum Eli E

BMC cancer 20140721

<h4>Background</h4>Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true preval ...[more]

PMID: 25047061

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Project description:BackgroundWe have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study.Methods and findingsWe genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y) from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012) kg/m(2) (p = 6.73 x 10(-37)) increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall). This association was significantly (p(interaction) = 0.005) more pronounced in inactive people (0.205 [SE 0.024] kg/m(2) [p = 3.62 x 10(-18); 592 g in weight]) than in active people (0.131 [SE 0.014] kg/m(2) [p = 7.97 x 10(-21); 379 g in weight]). Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26)) in the whole population, but significantly (p(interaction) = 0.015) more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16)]) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(-12)]). Consistent with the cross-sectional observations, physical activity modified the association between the genetic predisposition score and change in BMI during follow-up (p(interaction) = 0.028).ConclusionsOur study shows that living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity, as estimated by the number of risk alleles carried for any of the 12 recently GWAS-identified loci. Please see later in the article for the Editors' Summary.

Project description:Background Offering living kidney donation raised the concern that donors are exposed to unknown risks. All Swiss transplant centres therefore decided to start a prospective cohort study of living kidney donors in Switzerland. This paper describes the rationale for and implementation of this cohort study. Methods/design All kidney donors in Switzerland are registered and examined before donation and biennially after donation starting in the first year after nephrectomy. Before each follow-up visit, the study centre sends a package to the kidney donor containing the health questionnaire, blood and urine tubes and a prepaid envelope for sending the samples to the central laboratory. The donor makes an appointment with their family physician, who examines the donor and reports findings such as pain and other complaints, blood pressure, creatinine, albumin, all major health events and the state of mental and social well-being to the study centre. The family doctor draws the blood sample and mails it with the urine sample in the prepaid envelope. All data are centrally managed. All abnormal findings in the follow-up of individual donors are regularly discussed with the principal investigator, and necessary clinical changes made and recorded in the database. The health insurance of the recipient covers all costs of the donor follow-up. The main outcomes are the occurrence of albuminuria, hypertension and renal insufficiency. The secondary outcomes are major somatic and social events such as death, cardiovascular disease, stroke and depression. Discussion This prospective cohort offers unique opportunities to assess the risks of living kidney donation and will allow us to examine the risks associated with the methods used for nephrectomy in Switzerland (various forms of open surgery and laparoscopic nephrectomy). The prospective collection of all clinically relevant data and the regular monitoring of donors will allow timely interventions at early stages before serious kidney and general health problems occur.

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Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study.

Publications

Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study.

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