Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

In the PRS development 338,480 cases and controls from the UK Biobank + 3,650 cases and controls from the StoP consortium studies are going to be enrolled.

Cases are defined as primary gastric carcinoma patients, with histological confirmation.

Controls are selected from cancer-free patients matched with the cases.

In the analysis on the aetiology of Gastric Cancer 13,500 cases and 32,000 controls from the StoP consortium studies will be enrolled.

Cases are defined as primary gastric carcinoma patients, with histological confirmation.

Controls are selected from cancer-free patients matched with the cases.

Stefania Boccia, PhD

Roberta Pastorino, PhD

Gastric Cancer (GC) ranks fourth in the number of deaths worldwide and it is sixth in Italy with almost 9,000 deaths in 2020. Survival of GC is one of the lowest reported amongst major cancers, thus making prevention a central priority for its control. However there is currently a lack of evidence on gastric cancer determinants.

Our study will pursue the following specific objectives:

* analyze dietary and lifestyle habits for GC, also infrequent ones (WP1);
* analyze major risk factors in rare patient subgroups (WP2);
* develop a Genome-wide Modelling of polygenic risk score (PRS) in GC (WP3)

The Stomach cancer Pooling project (StoP) Consortium dataset has grown to the current number of 35 studies from Europe, America, Middle East and Eastern Asia. It will be used as the cornerstone upon which the investigation on the dietary and lifestyle determinants of gastric cancer (GC) will be built. It will allow the analyses of relatively infrequent habits or exposures, genetic factors as well as to perform sufficiently powered analyses of interactions and subgroups that may present relevant heterogeneity in the etiological correlates of GC.

The potential of genomics to personalize and thereby improve diagnosis, treatment, and prognosis of individuals has long been recognized, but so far evidence of the opportunity for genomics to drive prevention remains limited. Recent advances in research on Polygenic Risk Score (PRS) have created new interest about the use of genetic information in prevention of common diseases and its application to risk stratification. A long-lasting open question is whether common genetic variants used to build PRS are able to predict the risk of developing complex diseases with enough power to be used in a clinical setting.

The lack of large enough dataset able to allow an unbiased PRS validation, hampered this question to be answered for many years. This study builds upon the StoP project (a consortium collecting data from about 13,500 GC cases and 32,000 controls) and the UK Biobank (480 GC cases and 338,000 controls) to develop a Polygenic Risk Score for gastric cancer.

The study as a whole recruits a grand total of 383,980 participants but only genetic data from 342,130 individuals will be used.

This number can be further subdivided in:

* 3,650 participants enrolled in the Stomach Cancer Pooling Project (http://stop-project.org/) These biological samples will be processed to extract DNA data.
* 338,480 participants enrolled by the UK Biobank. These sample have already been processed. Informatized data from the biomarker samples will be used during the polygenic risk score development. For previously published details of UK Biobank, with anonymized data made available for researchers, please see: https://www.ukbiobank.ac.uk/enable-your-research/about-our-data/biomarker-data

Genomic and Dietary Aspects in Gastric Cancer Risk

Interaction of Genomic and Dietary Aspects in Gastric Cancer Risk: the Global StoP Project

Analysis of the association of dietary and lifestyle habits (e.g. caroteinoids, allium plant consumption, calcium, sodium intake, pipe and cigar smoking) from survey data with gastric cancer development

Analysis of the association between major risk factors in subgroups of studies or in rare patient groups (e.g.: gastric cancer in young people, cancer occurring at gastric cancer) and gastric cancer

Construction and evaluation of a PRS and a prediction model for gastric cancer, and evaluation of the performance in a validation sample

University of Bologna

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Full Professor of Hygiene and Preventive Medicine

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Cases are taken by recruiting women who:

* have no first degree family history of breast or ovarian cancer
* are or had been diagnosed with primary breast cancer or tested positive for high penetrance genes (e.g. BRCA 1/2)
* menarche age \>12 years old
* premenopausal

Controls are taken from clients who visited Breast Cancer Care Alliance (BCCA) and:

* have no family history of breast or ovarian cancer
* premenopausal
* menarche age \>12 years old
* asymptomatic
* do not have any first-degree relationship with the cases
* consented for the study and follow up

Genotyping of known breast cancer-related markers (313 variants) will be conducted using a microarray genotyping chip (Genetic Risk). Survey answers will determine Gail Model scores and thus Clinical Risk Score.

Breast Cancer Risk Prediction Software

Samuel Haryono, MD, PhD

Breast cancer is the most common cancer and cause of cancer- related deaths among women, accounting for 1.67 million (25.2%) new cases and 521,907 (14.7%) deaths worldwide. The prevalence and survival rates of breast cancer differ per country. In Indonesia, majority of patients (70.9%) go to the clinic with advanced stages of breast cancer. Five-year survival rate is 51.07%. One of the most important determinants of survival is education level and stage of breast cancer.

Current screening methods include mammography and radiology assessments, both of which have disadvantages specifically in Asian population. Mammography is less useful in Asian population because the population has denser breast, resulting to failure to diagnose cases of breast cancer in this population in 37-70% of cases. Moreover, screening methods provide binary answers, and therefore does not inform risk profile of the patients.

The investigators aim to implement PRS into the breast cancer screening process while observing the differences of genetic and non-genetic risk factor in patients with breast cancer and patients without any medical/family history of breast cancer in Indonesian population.

Breast cancer is the most common cancer and cause of cancer- related deaths among women, accounting for 1.67 million (25.2%) new cases and 521,907 (14.7%) deaths worldwide. The prevalence and survival rates of breast cancer differ per country. In Indonesia, majority of patients (70.9%) go to the clinic with advanced stages of breast cancer. Five-year survival rate is 51.07%. One of the most important determinants of survival is education level and stage of breast cancer.

Current screening methods include mammography and radiology assessments, both of which have disadvantages specifically in Asian population. Mammography is less useful in Asian population because the population has denser breast, resulting to failure to diagnose cases of breast cancer in this population in 37-70% of cases. Moreover, screening methods provide binary answers, and therefore does not inform risk profile of the patients.

Traditionally, risk prediction algorithms such as the GAIL model, BODACIEA, and Tyler-Cuzick use medical history and clinical factors of patients. However recently, genetics have grown in importance due to the heritability nature of cancer and availability of testing services and guidelines. About 10-30% of all cases are attributed to familial breast cancers, and of these, only 5%-10% correlate with hereditary factors linked with high penetrance. The most common genetic test to screen today is BRCA 1 and 2, and then other 22 genes curated by expert opinions on NCCN and other guidelines.

The prevalences estimated for carriers of mutations in BRCA1/2 are, respectively, 0.11% and 0.12% in the general population, and between 12.8%-16% in high risk families with three or more cases of breast or ovarian cancer. Approximately 10-15% of ovarian cancer cases are believed to be due to a BRCA1/2 mutation, however \~50% of individuals with a pathogenic BRCA mutation may not report a strong family history of cancer. NCCN, ASCO, St Gallen and has established guidelines to screen patients, but the low awareness in patients to go screening in the first place is hard.

Genetic testing using polygenic risk scores (PRS) combines the effects of low penetrance genes that together creates predictive value as strong as high-penetrance genes, but is much more common than high-penetrance gene testing. A PRS is most commonly calculated as a weighted sum of the number of risk alleles carried by an individual, where the risk alleles and their weights are defined by the loci and their measured effects as detected by genome wide association studies.

For some common adult-onset diseases, the polygenic risk conveyed to a substantial segment (10-20%) of the population whose genomes are enriched in risk alleles is comparable to the risk conveyed by commonly used clinical risk factors. A recent large-scale comprehensive GWAS for breast cancer found that 45% of familial relative risk of breast cancer can be explained by genetic variants captured by genotyping and imputation. As genotyping technologies advance, and consortia build algorithms on more samples, the predictive values of PRS algorithms are maturing. After analysis of 120,000 patients and optimizing for highest predictability, a PRS score combining 313 SNPs and clinical factors have a predictive value of 68%, compared to only 58% using clinical risk factors. A study conducted in the Breast Cancer Association Consortium showed that PRS combined with environmental risk factors can be used to distinguish women at different levels of breast cancer risk in the general population.

This score gives providers the opportunity to stratify the patients may result in some people with higher risk profile to start risk-reducing therapy earlier, start screening at a younger age, and modify their lifestyles with the aim of reducing their risk. For example, those who are at the top 1.5% of polygenic risk score have an odds ratio of 3 or more compared to the general population.

Polygenic risk scores have been applied in leading institutions in the world as clinical trials and in the commercial settings. However, there has been little application in developing countries to use polygenic risk score to increase awareness of risk-reducing strategies of breast cancer in patients.

One of the main concerns about the clinical implementation of population-based genetic screening is experts' availability post-test. A study in the UK for physicians' attitude towards risk stratification of ovarian cancer showed that 70% oncologists and 50% of GPs would be willing to offer genetic testing to their patients. About 60% believe that the test would give patients a sense of control, and over 80% of providers are willing to personalize recommendations based on risk stratification.

The investigators aim to implement PRS into the breast cancer screening process while observing the differences of genetic and non-genetic risk factor in patients with breast cancer and patients without any medical/family history of breast cancer in Indonesian population.

Genetic and Non-Genetic Breast Cancer Risk Prediction Evaluation in Indonesian Samples

Absolute non-genetic risk is calculated using the MDCalc Gail Model

Genetic risk is derived from polygenic risk score acquired from running a microarray sample result through an algorithm (see Mavaddat et al 2019)

SJH Initiatives

MRCCC Siloam Hospitals Semanggi

Nalagenetics Pte Ltd

Symptoms and General Pathology

Genetic Risk Score

Genetic Predisposition to Disease

Disease Susceptibility

Disease Attributes

Brigette Tippin-Davis, PhD

This study aims to assess how a polygenic risk score (PRS) reported with the results of multi-gene panel testing affects the breast cancer risk management recommendations healthcare providers make to their patients. The PRS is a score based on small genetic changes, clinical history, and family history. The PRS is used to estimate remaining lifetime risk of developing breast cancer for patients with no personal history of breast cancer and an overall negative result from MGPT.

Residual specimen may be maintained for an indefinite period of time at Ambry Genetics and be available for future studies as provided for in the consent document. Future studies on identifiable specimens or data will require review by an IRB or ethics committee.

Clinical Implementation of a Polygenic Risk Score (PRS) for Breast Cancer

Clinical Implementation of a Polygenic Risk Score (PRS) for Breast Cancer: Impact on Risk Estimates, Management Recommendations, Clinical Outcomes, and Patient Perception

Breast Cancer Risk Management Recommendations are recorded at two separate times; first recommendations will be recorded by the investigator or his/her designee based on the results of MGPT only. After these recommendations are recorded, the complete report including the PRS will be released. Then the healthcare provider will record recommendations again based on the results of MGPT and PRS. The difference between these recommendations will be used as a measure of the effect a PRS has on breast cancer risk management recommendations made by healthcare providers.

Ambry Genetics

Standard mammography screening in age 50-69

Mammography outside official screening

Peeter Padrik, MD, PhD

Vahur Valvere, MD,PhD

This is a cohort study, applied research and T3 translational genomics to estimate the impact of genetic risk for breast cancer detection in the screening program. The study group base consists of 28 389 female participants, currently in the age-group 22-79, in the Biobank of Estonian Genome Centre. The study is aimed to demonstrate the usability of personalised approach for adjusting and stratifying screening recommendations, based on predicted genetic risk estimates for breast cancer in the situation, where the genome data could be available from all women who have given informed consent for that. The project includes both the detection of moderate and high hereditary breast cancer risk carriers as well as high risk polygenic risk-score (consisting several single nucleotide polymorphisms) carriers among healthy individuals for application of personalised prevention and screening strategies.

Personalised Risk-based Breast Cancer Prevention and Screening

Implementation of a Model for Personalised Risk-Based Breast Cancer Prevention and Screening

University of Tartu

North Estonia Medical Centre

Tartu University Hospital

Director of the Cancer Center

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Exemestane

A Polygenic Risk Score (PRS) is a blood based genetic test which assesses 77 common breast cancer susceptibility loci (Single Nucleotide Polymorphisms). The PRS has been retrospectively validated and categorizes women into three categories of lifetime risk of developing breast cancer: Low Risk (\<15% lifetime risk), Above Average Risk (15 to 40%), and high risk (\>40%).

Polygenic Risk Score

Sandhya Pruthi, MD

The primary aim of this study is to determine if the addition of an individual polygenic risk score (PRS), in addition to the standard National Cancer Institute's Breast Cancer Risk Assessment Tool (BCRAT) or Tyrer-Cuzick (IBIS) score, will aid women at risk of breast cancer in making a decision to take (or not take) medications to prevent breast cancer

This trial is a prospective pilot study looking to integrate a novel and retrospectively validated polygenic risk score (PRS), based on 77 Single Nucleotide Polymorphisms (SNPs), into a standard breast cancer prevention consultation for non-BRCA women. In order to be eligible for trial participation, women will need to have a BCRAT estimate of ≥3% for the 5 year risk of developing breast cancer (which corresponds to the United States Preventative Services Task Force threshold for moderate to strong benefit from breast cancer preventing medications such as tamoxifen or raloxifene.

At the time of the breast cancer prevention consultation, women will be offered participation in this study by a clinical trials nurse and informed written consent will be obtained. For consenting patients, a single 7 to 10 ml blood sample will be taken and couriered to the MAYO clinic for sample analysis and several surveys will be administered. One of the surveys will assess the participants understanding and intention to take or not take breast cancer preventing medications. The decision to take or not take a breast cancer preventing medication will be deferred until a subsequent follow up visit.

On the second visit, the PRS test results will be reviewed with the patient and a recommendation regarding preventive medications will be made. The PRS score will risk stratify patients into one of three lifetime risk categories of developing breast cancer (low risk (\<15 % lifetime risk), above average risk (15 to \<40% risk) and high risk (\>40%)). Participants will then answer a second survey in which their understanding of their breast cancer risk and intention to take breast cancer preventing medications will be assessed.

Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake

Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake: A Pilot Study to Determine if a Polygenic Risk Score Influences the Decision to Accept Breast Cancer Preventive Medications (Tamoxifen, Raloxifene, or Exemestane) Amongst Non-BRCA Women at Risk

Functional Assessment of Cancer Therapy (FACT) - Endocrine Subscale Quality of Life Tool

CancerCare Manitoba

Mayo Clinic

Principal Investigator

Heart and Blood Diseases

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Coronary Artery Disease

Diabetes Mellitus, Type 2

Prostatic Neoplasms

Diabetes Mellitus

Atrial Fibrillation

Coronary Disease

Myocardial Ischemia

Colorectal Neoplasms

Ischemia

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Arrhythmias, Cardiac

Heart Diseases

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Patient-participants in the PRS-high arm and their providers will receive their high-PRS results at baseline, along with educational resources about the results.

Patient-participants in the UC-high arm and their providers will receive their high-PRS results after a 24-month observation period, along with educational resources about the results.

Patient-participants in the PRS-average arm and their providers will receive their average-PRS results at baseline, along with educational resources about the results.

Patient-participants in the UC-average arm and their providers will receive their average-PRS results after a 24-month observation period, along with educational resources about the results..

Polygenic risk score report from a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory for coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer (for women only), and prostate cancer (for men only), delivered along with patient- and provider-level educational material.

Polygenic risk score (PRS)

Jason L. Vassy, MD, MPH, SM

This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of prevalent or incident disease over 24 months.

One of the most pressing controversies in genomics today is the clinical utility of polygenic risk scores (PRS). Broadening the scope of genomic risk testing beyond monogenic diseases, PRS combine information from hundreds or even millions of genetic loci, each with a very small effect size on the risk of common complex disease. The result is a continuous quantitative risk factor for susceptibility to conditions such as coronary artery disease (CAD), type 2 diabetes (T2D), and breast cancer. Compared to rarer monogenic disease variants, PRS have greater transformative potential for public health and healthcare in their ability to identify much larger proportions of the population at significantly elevated risk for disease, facilitating evidence-based prevention and management. Moreover, their prediction ability has vastly improved compared to earlier PRS that included only a limited number of genetic variants. However, while the associations between PRS and a wide range of common diseases are well established (clinical validity), the potential impact of this information on patient health outcomes (clinical utility) remains contested and understudied.

This study will examine the effectiveness and implementation outcomes from the use of PRS for 6 common diseases that are screened for by PCPs and have established prevention strategies: CAD, AFib, T2D, colorectal cancer, prostate cancer, and breast cancer. This trial has two aims:

Aim 1: Conduct a randomized controlled trial (RCT) to determine the clinical effectiveness of PRS among patients at high genetic risk for at least one disease, measured by changes in clinical management (process outcomes) and time to diagnosis of prevalent or incident disease (clinical outcome) over 24 months.

Aim 2: Measure high-priority genomic medicine implementation outcomes, including primary care provider (PCP) knowledge and beliefs about PRS, patient activation in healthcare, medication adherence, and costs.

Randomized clinical trial comparing polygenic risk score (PRS) testing and reporting to delayed reporting

Participants are randomized to have them and their primary care providers receive their PRS results at baseline (PRS) or after 24 months (usual care, UC). Randomization is stratified by PRS results: A high-risk stratum consists of all participants with at least one PRS indicating high risk, while the remaining participants comprise the average-risk stratum. Participants who do not receive their results at baseline are blinded to whether they have all average-risk PRS results or any high-risk PRS results. Outcomes assessors and data analysts will be blinded to randomization and PRS results status.

The Genomic Medicine at VA Study

Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care

We will share de-identified individual-level trial data through a data repository housed on a secure VA server and accessible only to outside investigators with Institutional Review Board (IRB).

Semi-structured interviews will collect qualitative data on participating providers' understanding of and perceived utility of the PRS risk information.

The most recent systolic and diastolic blood pressure values recorded in the medical record prior to or on the date of enrollment and prior to or on the date 24 months after enrollment.

The most recent BMI values recorded in the medical record prior to or on the date of enrollment and prior to or on the date 24 months after enrollment.

Self-reported use of prescription or over-the-counter aspirin will be assessed on the baseline and end-of-study surveys.

Self-reported physical will be assessed on the baseline and end-of-study surveys using the Rapid Assessment of Physical Activity.

Self-reported alcohol will be assessed on the baseline and end-of-study surveys using measures from the Behavioral Risk Factor Surveillance System, recorded as an ordinal 5-item Likert response (from "Never" to "Very often").

Self-reported processed meat intake assessed on the baseline and end-of-study surveys using a food frequency question from National Cancer Institute Eating Habits Questionnaire, recorded as an ordinal 5-item Likert response (from "Never" to "Very often").

The most recent LDL-C values recorded in the medical record prior to or on the date of enrollment and prior to or on the date 24 months after enrollment.

Self-reported smoking status will be assessed on the baseline and end-of-study surveys using measures from the Behavioral Risk Factor Surveillance System.

Relevant prescription medication changes during 24-month observation period, including antihypertensives, cholesterol-lowering medications, anticoagulants, antiplatelet medications, 5-alpha reductase inhibitors, selective estrogen receptor modulators, aromatase inhibitors, as abstracted from medical record review.

As determined by data collected from the baseline survey (VR-12)

The primary outcome of the study is time-to-diagnosis both of undiagnosed prevalent cases of the 6 target conditions and incident cases during the study period. This composite outcome will only include clinically significant diagnoses, as adjudicated by expert clinical chart review.

Any evidence that the patient-participant underwent additional diagnostic testing for the six target diseases since enrollment: coronary artery disease (stress testing, cardiac CT for coronary artery calcium (CAC), coronary angiography), atrial fibrillation (ECG, heart rhythm monitoring), type 2 diabetes (hemoglobin A1c, blood glucose), colorectal cancer (colonoscopy, sigmoidoscopy, fecal blood testing, CT colonography), breast cancer (mammography, breast MRI, breast ultrasound, breast biopsy), and prostate cancer (PSA testing, prostate biopsy).

Self-reported understanding, competence, and willingness to participate health care decisions and processes assessed on the baseline and end-of-study surveys, using the 13-item short form of the Patient Activation Measure (Hibbard, Health Services Research 2005).

A combination of administrative data and microcosting approaches will be used to estimate the costs of the intervention and the subsequent patient-level healthcare costs over the 24 months after enrollment. Estimates of the infrastructure and personnel needed to deliver the intervention will be derived empirically from the study. Healthcare costs will be abstracted from billing and administrative data.

Self-report of taking medications as prescribed assessed on the baseline and end-of-study surveys, using the 3-item Voils Medication Adherence Survey (Voils, Medical Care, 2012).

VA Boston Healthcare System

Boston VA Research Institute, Inc.

Participants are placed into their arm after appropriate genetic testing has been conducted to determine their risk.

Participants will be put into PRS cohorts based on their genetic data.

All participants enrolled into the study will receive a PSA screening test and an mpMRI, regardless of their polygenic risk score.

Polygenic Risk Score (PRS)

Adam S Kibel, MD, MHCM

Daniella Furtado

Pamela Coleman, MD

Tamaro S Hudson, PhD, MPH

Peter A Pinto, MD

Ismail B Turkbey, MD

Peter L Choyke, MD, FACR

Gregory T Chesnut, MD

Peter Pinto, MD

The goal of this clinical trial is to evaluate a screening method to detect clinically relevant prostate cancer. This clinical trial is using genetic data to determine a man's risk of cancer, together with multiparametric magnetic resonance imaging (mpMRI) to identify men with higher grade cancer.

The main questions it aims to answer are:

* If genetic data related to prostate cancer used with MRI can identify higher-grade, potentially fatal prostate cancer
* What age a MRI is useful clinically for prostate cancer screening
* If deep learning methods used with MRI when the genetic risk of the man is known can more accurately predict significant cancers

Participants will:

* Get a prostate specific antigen (PSA) blood test
* Get an mpMRI
* Get the results of their genetic data to determine if they are considered high-, intermediate-, or low-risk for prostate cancer based on the trials genetic testing
* Follow-up for this trial based on the participants risk and findings from the PSA test and mpMRI

Background:

* Prostate cancer is the most commonly diagnosed cancer among men in the United States
* Prostate cancer screening using the marker prostate-specific antigen (PSA) is controversial
* PSA based screening is less effective, at least in part, because it rests on screening the entire population
* Polygenic risk scores stratify men based on their prostate cancer genetic predisposition and may improve population level screening programs by focusing on men with higher risk of disease and sparing low risk men
* It is critical that studies aiming to translate the development of an early-detection strategy are conducted within a diverse patient population to address prostate cancer mortality disparities

Study Design:

* Plan to accrue 1,500 participants from both established biobanks and primary care offices
* Participants will get an initial PSA screening blood test and an mpMRI
* Participants will have their polygenic risk score determined from genome-wide association study (GWAS) data
* Participant follow-up will be determined by PRS results, as well as if there are abnormal findings on their PSA screening and/or mpMRI

Objectives:

* To evaluate a screening algorithm to detect clinically relevant prostate cancer (Gleason score ≥7) using genetic data (PRS) to determine risk of cancer and mpMRI to identify men with higher grade cancer
* To determine optimal age to begin screening using PRS and mpMRI
* To determine if rare variants in DNA repair enzymes could help refine screening
* To determine if deep learning methods applied to mpMRI and informed by genetic risk can more accurately predict significant cancers

Prostate cancer screening using prostate specific antigen (PSA) is controversial. On the one hand, there is a reduction in prostate cancer mortality associated with screening. On the other, there is clear evidence that widespread and indiscriminate PSA based screening has led to over diagnosis and over treatment of prostate cancer. In part this is due to indiscriminate screening of all men, not just those at risk. Development and implementation of a screening strategy specifically targeting men at risk for potentially harmful prostate cancer, while sparing low risk men the burdens of screening, is urgently needed.

The investigators believe that integration of genetic testing and multiparametric MRI (mpMRI) will dramatically improve screening. Polygenic risk scores (PRS) have been developed to determine an individual's risk of prostate cancer and attempts have been made to create risk scores for clinically relevant disease. mpMRI has been established as an aid in differentiating clinically relevant from indolent prostate cancer.

Our scientific premise is that an integrated approach which leverages the strengths of both genetics and mpMRI will do more than simply risk stratify men into those at risk for and not at risk for prostate cancer; the investigators will stratify a population of men into those with and those without clinically relevant prostate cancer. The investigators hypothesize that genetic testing to first identify patients at risk of prostate cancer followed by mpMRI to determine who likely has clinically relevant disease represents an optimal strategy.

This study will determine if a polygenic risk score can be used in conjunction with mpMRI to identify Gleason score ≥7 cancer.

Polygenic Risk Stratification Combined With mpMRI to Identify Clinically Relevant Prostate Cancer

The ratio between men with high PRS and intermediate PRS in each of the three age groups (40-54, 55-64, 65-69) regardless of their ethnicity.

The ratio between men with high PRS and intermediate PRS in each of the six age groups (40-44, 45-49, 50-54, 55-59, 60-64, 65-69) regardless of their ethnicity.

Examine the extent to which the addition of rare variants to the PRS involves risk prediction. The weighting procedure will be implemented to account for oversampling of high risk cases.

National Cancer Institute (NCI)

Adam S. Kibel, MD

Chair, Department of Urology, Brigham Health & Dana-Farber Cancer Institute; DiNovi Family Distinguished Chair in Urology, Brigham and Women's Hospital; Elliott Carr Cutler Professor of Surgery, Harvard Medical School

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genomic and Dietary Aspects in Gastric Cancer Risk	NCT05934058	Gastric Cancer		18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Genetic and Non-Genetic Breast Cancer Risk Prediction Evaluation in Indonesian Samples	NCT05570266	Breast Cancer	Breast Cancer R...	35 Years - 75 Years	Nalagenetics Pte Ltd
Clinical Implementation of a Polygenic Risk Score (PRS) for Breast Cancer	NCT03688204	Breast Cancer R...		18 Years -	Ambry Genetics
Personalised Risk-based Breast Cancer Prevention and Screening	NCT03989258	Breast Cancer	Mammography out...	25 Years -	Tartu University Hospital
Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake	NCT02517593	Breast Cancer	Polygenic Risk ...	35 Years - 75 Years	Mayo Clinic
The Genomic Medicine at VA Study	NCT04331535	Coronary Artery... Atrial Fibrilla... Type 2 Diabetes Colorectal Canc... Breast Cancer Prostate Cancer	Polygenic risk ...	50 Years - 70 Years	Boston VA Research Institute, Inc.
The Genomic Medicine at VA Study	NCT04331535	Coronary Artery... Atrial Fibrilla... Type 2 Diabetes Colorectal Canc... Breast Cancer Prostate Cancer	Polygenic risk ...	50 Years - 70 Years	Boston VA Research Institute, Inc.
Personalised Risk-based Breast Cancer Prevention and Screening	NCT03989258	Breast Cancer	Mammography out...	25 Years -	Tartu University Hospital
Genomic and Dietary Aspects in Gastric Cancer Risk	NCT05934058	Gastric Cancer		18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Polygenic Risk Stratification Combined With mpMRI to Identify Clinically Relevant Prostate Cancer	NCT06398639	Prostate Cancer Polygenic Risk ...	Polygenic Risk ...	40 Years - 69 Years	Brigham and Women's Hospital
Clinical Implementation of a Polygenic Risk Score (PRS) for Breast Cancer	NCT03688204	Breast Cancer R...		18 Years -	Ambry Genetics

Spots Global Cancer Trial Database for polygenic risk score