Mutations in the PALB2 gene confer as much increased risk for breast
cancer as BRCA2 mutations, according to a New England Journal of
Medicine study. The PALB2 protein is key to several BRCA2 functions,
including limiting cellular DNA damage.

U.K. researchers examined breast cancer risk among some 360 members of
154 families in which at least one person had breast cancer and a loss-
of-function mutation in PALB2 (but no BRCA mutations). They found that
breast cancer risk was 9.5 times higher among mutation carriers than
in the general population. The absolute breast cancer risk by age 70
among women with PALB2 mutations ranged from 33% among those with no
family history of breast cancer to 58% among those with at least two
first-degree relatives with breast cancer at age 50. PALB2 mutations
also increased risk among men.

The researchers say the level of risk conferred by PALB2 mutations
would be considered high according to American Cancer Society and
other guidelines. “This level of risk,” they write, “may justify
adding PALB2 to genetic testing for BRCA1 and BRCA2.”

New England Journal of Medicine