Rare mutations in PALB2, CHEK2, and ATM: how much do they increase cancer risk?
https://www.facingourrisk.org/XRAY/rare-mutations-and-cancer-risk
Full article: http://jmg.bmj.com/content/early/2016/09/02/jmedgenet-2016-103839.short?rss=1
As multi-gene panel tests become more common, people are discovering they have mutations in genes that are not understood as well as BRCA. This can make it difficult to give patients accurate assessments of their cancer risk. For example, mutations in PALB2, CHEK2, and ATM are rare, but some specific changes in these genes are even less common. The goal of this international collaboration was to better understand the cancer risks of some very rare PALB2, CHEK2, and ATM mutations. The findings are relevant only to the specific mutations covered in this paper and do not apply to all people with mutations in PALB2, CHEK2, or ATM. (9/27/16)
Questions To Ask Your Health Care Provider
- I was diagnosed with breast cancer before age of 45; should I consider genetic testing?
- I tested negative for mutations in BRCA1 and BRCA2, despite being diagnosed with breast cancer before the age of 45; should I consider additional genetic testing?
- Members of my family have a mutation in PALB2, CHEK2, or ATM; should I consider genetic testing?
- I tested positive for a mutation in a gene for which cancer risk is not well understood; how can I be sure I get new information on my cancer risk as more research is completed?
- Can you refer me to a genetics expert?
Open Clinical Trials
The following are risk-management studies enrolling people with inherited mutations. Check study listings or contact the study team to see if you are eligible.
Multiple cancers
- NCT02665195: Prospective Registry Of MultiPlex Testing (PROMPT). PROMPT is an online research registry for people who have had genetic panel testing. The goal of the PROMPT Registry is to follow people with mutations or variants in genes on these panels, so that patients, physicians and researchers can more clearly understand these lesser-known risks. This study is open to people with an inherited mutation or VUS in a number of different genes, including: ATM, BRIP1, CHEK2, PALB2, PTEN, RAD51C, RAD51D and others.
- The Risk Factor Analysis of Hereditary Breast and Ovarian Cancer In Women with BRCA1, BRCA2 or PALB2 Mutations This study seeks to improve researchers’ understanding of how hormonal, reproductive and lifestyle factors may be associated with cancer in this high-risk population.
Prostate cancer
- NCT03805919: Men at High Genetic Risk for Prostate Cancer. This is a prostate cancer screening study using MRI in high risk men. This study is open to men with ATM, BRCA1, BRCA2, BRIP1, CHEK2, HOXB13, Lynch syndrome, NBN, RAD51D, TP53 and other inherited mutations.
- NCT05129605: Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS). This study will look at how well prostate MRI works as a screening tool for men at high risk for prostate cancer. This study is open to men with inherited mutations in ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D, TP53 and other genes.
Ovarian cancer
- Validating a Blood Test for Early Ovarian Cancer Detection in High-risk Women and Families: MicroRNA Detection Study (MiDE). The goal of MiDe is to develop a test to detect ovarian cancer. Participants can be expected to provide up to 4 tubes of blood every 6 months for up to 5 years. We can collect these samples through mobile phlebotomy all around the US. The study is enrolling people with BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, Lynch syndrome and other mutations.
- NCT05287451: Risk Reducing Salpingectomy With Delayed Oophorectomy as an Alternative to Risk- Reducing Salpingo-oophorectomy in High Risk-Women to Assess the Safety of Prevention. This study will look at outcomes in women with BRCA1, BRCA2, BRIP1, RAD51C and RAD51D who remove their fallopian tubes first, followed by removal of their ovaries compared to women who undergo standard-of-care removal of their ovaries and fallopian tubes at the same time.
Pancreatic cancer
- NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer. MRI and Magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for early stage pancreatic lesions.
- NCT02206360: Pancreatic Cancer Early Detection Program. This pancreatic cancer screening study uses esopheal ultrasound to screen for pancreatic cancer in high risk people. The study is open to people who have an inherited mutation in one of the following genes: ATM, BRCA1, BRCA2, CDKN2A, PALB2, STK11 or Lynch syndrome.
- NCT03568630: Blood Markers of Early Pancreas Cancer. This pancreatic cancer study involves blood samples over time to look for biomarkers of pancreatic cancer in high risk people. The study is open to people with a mutation linked to increased cancer risk.
- NCT02478892: Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with an Inherited Genetic Risk Due to a BRCA1, BRCA2, PALB2 or ATM Mutation. This study uses MRI and endoscopic ultrasound to screen for pancreatic cancer in people with a BRCA1/2, PALB2 or ATM mutation.
Additional risk-management clinical trials for people with inherited mutations may be found here.
About FORCE
FORCE is a national nonprofit organization, established in 1999. Our mission is to improve the lives of individuals and families affected by adult hereditary cancers.