Population Based Germline Testing for Early Detection and Prevention of Cancer

NCT07498829 | Recruiting

• 2 other identifiers: IRAS 328404REC Reference 24/NW/0294
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 1

Brief Summary

PROTECT-C is a research study offering genetic testing to people to see whether they have a genetic change that increases their risk of breast, ovary, bowel, and/or womb cancer. This is regardless of whether they or their families have had cancer. Breast, ovary, bowel, and womb cancers make up half of all cancers in women. Around 15-20% (15 to 20 in 100 cases) of ovary and 3-4% (3 to 4 in 100 cases) of breast, womb, and bowel cancers are linked to cancer genes and may be prevented. People with a genetic change that puts them at increased risk of any of these cancers have ways to help them manage their risk through the NHS. This may include screening to find cancers earlier when they are easier to treat, and surgery or medication to prevent cancers from developing. This can save lives. Currently, genetic testing is only available on the NHS to people who meet certain criteria. For example, those who have had certain cancers, have a strong family history of cancer, or those with Jewish ancestry. But many people may not have a strong family history or meet NHS testing criteria. This means that this system of testing misses 50% to 80% of people (50 to 80 in 100 people) who have a genetic change. It is thought that only around 3 in 100 people overall who have a genetic change that increases their risk of cancer know about it. Given the effective screening and preventive options that are available, this represents a huge, missed opportunity to prevent cancers or find them earlier. The PROTECT-C study aims to evaluate the option of offering genetic testing to everyone who may want it. This is regardless of whether they or their families have had cancer. We will offer genetic testing to 5000 people. People may take part if they:

• Are over the age of 18 years and
• Are a woman, trans man, or non-binary person with female reproductive organs (ovaries, fallopian tubes, and/or a uterus) and
• Have never had genetic testing for the cancer genes tested for in the study and
• Do not have first-degree family members (e.g.: parent, sibling, child) or second-degree family members (e.g.: aunt, uncle, niece, nephew, grandchild, grandparent, half-sibling) with genetic changes in the cancer genes tested for in the study PROTECT-C is a completely digital study. The study team will give participants access to an app developed specifically for this study. They can download this app using a smartphone or tablet or access it on any internet browser using a computer or laptop. Before they can access the app, participants will need to complete a consent form. They will also be asked to fill in a short questionnaire about themselves and their health. The PROTECT-C app contains information to help participants decide if they would like to have genetic testing. If they decide to have genetic testing, they will complete a consent form for genetic testing on the app. The study team will send them a saliva based test kit in the post. The study will look at how many people decide to have genetic testing and how many of them are found to have a genetic change. It will evaluate their experience with using the app and how this approach to genetic testing affects their quality-of-life, satisfaction, and mental well-being. This will give us a better understanding of how well the app works as a way of offering genetic testing to people. The study is interested to see how people found to be at increased risk decide to manage their risk. We will assess the uptake of screening and prevention options. Few participants will be invited to have 1:1 interviews by the study team. This will evaluate their experience of making a decision about genetic testing and taking part in the study. Taking part in these interviews is optional. The study will also assess if this way of offering genetic testing to people is affordable for the NHS.

Conditions

Breast Cancer Risk; Ovarian Cancer Risk; Cancer Gene Mutation

Keywords

Population based genetic testing; BRCA; Lynch Syndrome; breast cancer risk; ovarian cancer risk

Outcome Measures

Primary Outcomes (1)

• Pathogenic variant (PV) prevalence for multiple moderate to high penetrance CSGs (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) in women from unselected population-based genetic testing compared with FH-based genetic testing

  The primary outcome measure is the proportion of women with one or more CSGs who have undergone genetic testing and received a valid result. PV prevalence will be estimated by the number of observed PVs divided by the total number of individuals tested. An overall rate and CSG specific rates will be calculated. Standard NHS criteria at time of the study (i.e. Amsterdam-2 Criteria for Lynch Syndrome and 10% BRCA probability threshold for HBOC) will be used to evaluate family history criteria for genetic testing. The proportion of PVs fulfilling NHS testing criteria (FH positive) will be estimated. 95% Confidence Intervals for these outcomes will be calculated as per methods specified in the SAP (statistical analysis plan).

  1 year after completing recruitment

Secondary Outcomes (12)

• Satisfaction and regret (Satisfaction)

  measured at acceptance, 21 days, 6 months and 12 months

• Satisfaction and regret (Regret)

  measured at acceptance, 21 days, 6 months and 12 months

• Quality of life using EQ5D- 5L

  Pre-genetic testing and at 21 days, 6 months and 12 months

• Psychosocial wellbeing - Cancer worry

  Pre-genetic testing and at 21 days, 6 months and 12 months

• Psychosocial wellbeing - Risk perception

  Pre-genetic testing and at 21 days, 6 months and 12 months

Other Outcomes (23)

• To determine the uptake of population-based genetic testing

  6 months after return of the last test result

• Proportion of women categorised as moderate and high risk of breast cancer (BC) and moderate and moderate and high risk of ovarian cancer (OC)

  6 months after return of the last test resut.

• PV prevalence for individual CSG : BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6

  6 months after return of the last test result.

Study Arms (1)

Genetic testing

EXPERIMENTAL

Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk prediction

Genetic: Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk

Interventions

Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk GENETIC

Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk for all women (including trans-men, and non-binary individuals with female reproductive organs) over the age of 18 years independent of any family or personal history of cancer.

Genetic testing

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women, trans men, and non-binary people with female reproductive organs who are ≥18 years at consent
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women, trans men, and non-binary people with female reproductive organs
• ≥18 years at consent

You may not qualify if:

• Individuals who have previously undergone genetic testing for one or more of the following CSGs: BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BRIP1, MLH1, MSH2, MSH6
• One or more first- or second-degree relative with a PV in any of above CSGs
• Inability to provide informed consent

Sponsors & Collaborators

• Queen Mary University of London: lead
• University of Cambridge: collaborator
• University of Manchester: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Institute of Cancer Research, United Kingdom: collaborator
• University of Leeds: collaborator
• Imperial College London: collaborator
• University College, London: collaborator
• VU University Medical Center (VUmc): collaborator
• St George's, University of London: collaborator

Study Sites (1)

Wolfson Institute of Population Health, Queen Mary University of London

London, EC1M 6BQ, United Kingdom

RECRUITING

Related Links

• PROTECT-C Web site

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Genetic Testing; RAD51C protein, human; G-T mismatch-binding protein

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Ranjit Manchanda, PhD

  Wolfson Institute of Population Health, Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ranjit Manchanda, PhD

CONTACT

+44 8008620236; r.manchanda@qmul.ac.uk

Caitlin Fierheller, PhD

CONTACT

+44 8008620236; protectc.study@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional cohort study offering genetic testing for moderate to high penetrance Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and a personalised breast and ovarian cancer risk prediction using a digital app and saliva based DNA testing.

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: March 27, 2026
• Study Start: December 18, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2040
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

GB (1)