Rare mutations in PALB2, CHEK2, and ATM: how much do they increase 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)
The National Comprehensive Cancer Network (NCCN) brings together a panel of experts to create guidelines for genetic testing for inherited mutations that increase cancer risk. NCCN Guidelines for women with mutations in PALB2, NBN, BRIP1 and other genes include the following:
Breast Cancer Screening:
- Annual screening mammogram (consider 3D mammography) and annual MRI with contrast beginning at age 30, or earlier based on family breast cancer history for women with mutations in following genes:
- Annual screening mammogram (consider 3D mammography) and annual MRI with contrast beginning at age 40, or earlier based on family breast cancer history for women with mutations in following genes:
Breast Cancer Risk Management
- Discussing the option of risk-reducing mastectomy based of family history of breast cancer for women with mutations in:
It is important for people with mutations in these genes to consult with a genetics expert to determine the best risk management plan based on their personal and family medical history and other circumstances.
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
- NCT02665195: Prospective Registry of Multiplex Testing (PROMPT). This study is being done to learn more about how changes in certain genes may be linked to cancer. The want to better understand the risks that are linked to genetic changes in these less well-studied genes in order to give better advice to families with mutations in these genes.
- Breast Cancer Treatment in Women with PALB2 Mutations. The PALB2 Study is an international research study to better understand breast cancer treatment among women with a PALB2 gene mutation. Participants are asked to complete online or paper study questionnaires (every two years for 10 years) and share their family history, medical, and genetics records.
- NCT03805919: Men at High Genetic Risk for Prostate Cancer. The National Cancer Institute recently opened a clinical trial for prostate cancer screening in men who may be at high risk for prostate cancer due to an inherited mutation in BRCA1, BRCA2, HOXB13, ATM, NBN, TP53, Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM), CHEK2, PALB2, RAD51D, or FANCA.
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.