Download PALB2 and Family History

PALB2, Family History, & Cancer Risks
By Jacqueline Mersch, MS, CGC
Certified Genetic Counselor
UT Southwestern Medical Center
If you find a mutation in a gene associated with hereditary cancer then you know the cancer
risks, right? Actually, the risk is not as clear cut as once thought. Family history can impact the
cancer risk for an individual with a genetic mutation. Family members share multiple factors
that can adjust their cancer risk including other genetic similarities, environment, and lifestyle.
One example of a gene impacted by family history of cancer is the PALB2 gene. Recently, PALB2
has been getting more attention in the media because of its link to breast cancer and new
research on the risk.
The PALB2 official gene name is “partner and localizer of BRCA2.” As the name suggests, the
gene is directly involved with the BRCA2 pathway of DNA damage repair. DNA damage from
cellular metabolism, environmental exposures, and lifestyle factors accumulates over time if
not repaired. DNA damage can lead to genomic instability, unregulated cell growth and
proliferation, and ultimately tumor formation. PALB2 is part of a protein complex with BRCA2
and RAD51C that suppresses tumors by repairing DNA damage. Mutations in the PALB2 gene
affect the cell’s ability to repair DNA damage and increase the risk for tumors.
Individuals with a mutation in the PALB2 gene have an increased lifetime risk for breast and
pancreatic cancer, and may have elevated risk for other cancers. Originally, the general risk for
female breast cancer associated with a PALB2 mutation was two to four times the general
population risk of breast cancer. In a recent article, Antoniou et al. researched the impact of
family history on the magnitude of breast cancer risk in families with a PALB2 mutation. If a
woman with a PALB2 mutation has a strong family history of breast cancer (2 or more relatives
with breast cancer by age 50), her lifetime breast cancer risk could be as high at 58%. If a
woman with a PALB2 mutation does not have a family history of breast cancer, her lifetime
breast cancer risk was estimated to be 33%. Men with a PALB2 mutation may have an increased
risk for breast cancer compared to the general population. The lifetime risk for pancreatic
cancer in men and women with PALB2 mutations is also increased compared to the general
population risk, although the magnitude of increase remains unclear.
Panel tests for hereditary cancer predisposition genes often include the PALB2 gene. However,
specific screening and management guidelines for PALB2 mutations have not been established
at this time. Surveillance recommendations are currently based on other guidelines for
comparable risks (i.e. BRCA1/BRCA2 breast cancer risk management). High risk breast cancer
screening for women including mammograms and breast MRIs are recommended with
consideration for prophylactic surgery. Specific screening guidelines for increased pancreatic
cancer risk are not available but various imaging techniques could be considered.
Increased uptake of panel testing and identification of PALB2 mutations in individuals means
you may see more of these women and families in your practice. It is important to be aware of
the cancer risks associated with a genetic mutation. Keep in mind the utility of family history to
individualize the risk for a PALB2 mutation carrier emphasized by the latest research. PALB2 is
one example of several genes known to have cancer risk estimates modified by family history.
Furthermore, the lifetime risk estimates and clinical management guidelines will continue to
evolve over time as more information is gleaned from families with PALB2 mutations. As
always, please contact the genetics office with any questions at 817-288-9800.
Antoniou AC, et al. Breast-Cancer Risk in Families with Mutations in PALB2. N Engl J Med
2014;371(6):497-506.