Inherited mutations, PALB2, risk, cancers, treatment and resources

Inherited mutations, PALB2, risk, cancers, treatment and resources

PALB2 refers to a gene in the DNA and a protein derived from that gene. Inherited mutations in PALB2 (or, Partner and Localiser of BRCA2) are associated with an increased risk of breast cancer, ovarian cancer, some blood cancers and pancreatic cancer.


BRCA1 and BRCA2 inherited mutations


Approximately seven percent of people walking around today in the Western world have an inherited mutation and most will not know until they develop cancer and, even then, few people are tested - women with breast and ovarian cancer being most likely, It is thought that this seven percent of women may account for 40% of breast cancers. Clearly, until everyone with cancer is tested, neither the numbers of people nor the full list of cancers will be known.

To cover PALB2, we must first touch on the two more common inherited mutations. 

BRCA1 is a protein coded by the BRCA1 gene, which is a human suppressor gene responsible for repairing DNA. It is also called a ‘protector gene’. BRCA1 is associated with certain polymerases which are responsible for gene repair by helping to rewrite genetic code from RNA copies previously made.

BRCA2 is a separate protein coded by the BRCA2 gene. It is also a DNA repair gene.

These are inherited mutations; also called germline mutations or variants. If you have inherited either of these mutations from a parent, you will still have the healthy gene in the other DNA strand from the other parent,

While it is estimated in the USA that 13% of women will develop breast cancer at some point in their lives, this rises to 55%–72% of women with a faulty BRCA1 variant and 45%–69% of women with a faulty BRCA2 variant (1).

In Ovarian cancer, the respective figures are 1.2%, 39-44% and 11-17%.

BRCA1 and BRCA2 are denoted this way because they were first discovered as BReast cancer risks. Even haematologic cancers have been shown as a higher risk in people with these inherited mutation (2). And more than 8% of child cancers were found to be in children with inherited mutations, even though the form of cancer did not run in the family (3). This may be because of their multifunctionality; for example, at least one function of these inherited genes is to repair double strand breaks, which might lead to any cancer. 

BRCA1, BRCA2 and PALB2 variations are also associated with pancreatic cancer risk (4).

The PALB2 interaction in gene repair

One in 700-1000 people carry a PALB2 mutation. PALB2 was originally identified by Prof David Livingston at the Dana-Farber Cancer Institute; its protein normally interacts with BRCA2 to aid DNA repair. According to Dana-Faber, finding a PALB2 mutation makes a PARP inhibitor a treatment option (5). 

A study in the New England Medical Journal showed that inheriting a PALB2 mutation makes a woman 36% more likely to develop breast cancer, because of the essential interaction between a healthy PALB2 protein, and a healthy BRCA2 protein in DNA repair (6). 

If a person has the PALB2 variation they are termed a carrier; if they have children with another carrier, there is a one-in-four chance of them having a child with Fanconi anaemia, a very rare blood disorder; the majority develop liver tumours or AML (leukaemia) by the time they are 40. Endocrine problems are also common (7).

PALB2 UK Resources

There is a special PALB2 website (8) covering everything from TV Presenter Sarah Beeney’s journey with PALB2 breast cancer, to a family where three sisters all carry the PALB2 mutation. It involves various international experts.

In the UK, Marc Tischkowitz is a Professor of Medical Genetics at Cambridge University and a number of people work with him there on PALB2 research.

PALB2 and PARP inhibitors

PARP inhibitors are now commonly used for people with BRCA1 and BRCA2 mutations. It was no surprise therefore to see one tested, and successfully, with PALB2 patients. Using the PARP inhibitor Olaparib, researchers achieved a ‘dramatic’ response (9).

Another trial used the PARP inhibitor Talazoparib successfully (10).

We have a lot of information on CANCERactive and PARP inhibitors with people who have cancer and a genetic mutation. For example: 


Go to: Gene Mutations like BRCA 1,  BRCA 2 and PALB2 and your increased risk of cancer


Go to: BRCA1 and BRCA2 and PARP inhibitors


Go to: Having an inherited genetic mutation makes no difference to your odds of survival with breast cancer


Go to: PARP inhibitors - What supplements may help; from Research




  1. National Cancer Institute - BRCA Gene Mutations: Cancer Risk and Genetic Testing

  2. The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers; Bernard Friedenson; BMC Cancer. 2007; 7: 152.

  3. Germline Mutations in Predisposition Genes in Pediatric Cancer; Jinghui Zhang et al; December 10, 2015, N Engl J Med 2015; 373:2336-2346

  4. Genetics and Hereditary Factors of Pancreatic cancer - Pancreatic Cancer Action Network

  5. PALB2 Breast Cancer Gene: What You Should Know; Blog November 9 2021

  6. What You Need to Know About the PALB2 Breast Cancer Gene; October 2021, Yale School of Medicine

  7. Wikipedia - 

  8. PALB Interest group, UK - 

  9. Dramatic response to PARP inhibition in a PALB2-mutated breast cancer: moving beyond BRCA; T Grellety et al; Ann Oncol; 2020 Jun;31(6):822-823.

  10.  A phase II clinical trial of talazoparib monotherapy for PALB2 mutation-associated advanced breast cancer; Joshua James Gruber et al; Journal of Clinical Oncology; Vol 39, Issue 15




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