Hungarian Scientific Research Grant(NRDI FK135065)
New National Excellence Program of the Ministry of Human Capacities(UNKP-22-5-SE-1)
(Bolyai Research Fellowship of the Hungarian Academy of Sciences)
National Laboratories Excellence program (under the National Tumor Biology Laboratory
Project(NLP-17)
Background: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile
of PALB2, the third most important breast cancer gene, may vary between different
populations. Methods: PALB2 was analyzed in peripheral blood samples of three independent
cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive
patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other
cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years,
yBC) patients. These data were compared with data of 134,187 non-cancer individuals
retrieved from the Genome Aggregation Database. Results: Altogether, 235 cases (235/1280;
18.3%) carried at least one P/LP variant in one of the HBOC susceptibility genes.
P/LP PALB2 variants were identified in 18 patients (1.4%; 18/1280) in the HBOC and
3 cases (1.5%; 3/191) in the yBC group. In the control group, only one patient had
a disease-causing PALB2 variant (0.17%; 1/568) as a secondary finding not related
to the disease, which was similar (0.15%; 205/134,187) in the non-cancer control group.
The NM_024675.4:c.509_510delGA variant was the most common among our patients (33%;
6/18). We did not find a significant difference in the incidence of PALB2 disease-causing
variants according to age; however, the median age of tumor onset was lower in PALB2
P/LP carriers versus wild-type patients (44 vs. 48 years). In our cohort, the odds
ratio for breast cancer risk in women with PALB2 P/LP variants was between 8.1 and
9.3 compared to non-HBOC cancer patients and the non-cancer population, respectively.
Conclusions: PALB2 P/LP variants are not uncommon among breast and/or ovarian cancer
patients. Their incidence was the same in the two breast cancer cohorts studied but
may occur rarely in patients with non-breast/ovarian cancer. The c.509_510delGA variant
is particularly common in the studied Hungarian patient population.
