Population Based Germline Testing for Early Detection and Prevention of Cancer

Overview

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.

Interventions

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

Primary outcome measures

• 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 [Time frame: 1 year after completing recruitment]

Secondary outcome measures (12)

• Satisfaction and regret (Satisfaction) [Time frame: measured at acceptance, 21 days, 6 months and 12 months]
• Satisfaction and regret (Regret) [Time frame: measured at acceptance, 21 days, 6 months and 12 months]
• Quality of life using EQ5D- 5L [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Psychosocial wellbeing - Cancer worry [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Psychosocial wellbeing - Risk perception [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Psychosocial wellbeing - Anxiety and depression [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Psychosocial wellbeing - Distress [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Psychosocial wellbeing - Impact [Time frame: Pre-genetic testing and at 21 days, 6 months and 12 months]
• Uptake of risk management options [Time frame: collected annually over 8 years]
• Uptake of cascade testing [Time frame: 2 years post return of last result in those recruited]
• VUS carrier frequency [Time frame: 6 months after return of the last test result]
• Cost-effectiveness of genetic testing [Time frame: 12 months after return of last test result - initial analysis]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United Kingdom · 1 center

• Wolfson Institute of Population Health, Queen Mary University of London — London

Identifiers

NCT: NCT07498829 · IRAS 328404 · REC Reference 24/NW/0294

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗