Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

Abstract

PALB2-mutation carriers not only have an increased risk for breast cancer (BC) but also for pancreatic cancer (PC). Thus far, PALB2 mutations have been mainly found in PC patients from families affected by both PC and BC. As it is well known that the prevalence of gene mutations varies between different populations, we studied the prevalence of PALB2 mutations in a Dutch cohort of non-BRCA1/2 familial PC (FPC) families and in non-BRCA1/2 familial BC (FBC) families with at least one PC case. Mutation analysis included direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and was performed in a total of 64 patients from 56 distinct families (28 FPC families, 28 FBC families). In total, 31 patients (48%) originated from FPC families; 24 were FPC patients (77%), 6 had a personal history of BC (19%) and 1 was a suspected carrier (3.2%). The remaining 33 patients (52%) were all female BC patients of whom 31 (94%) had a family history of PC and 2 (6.1%) had a personal history of PC. In none of these 64 patients a PALB2 mutation was found. Therefore, PALB2 does not have a major causal role in familial clustering of PC and BC in non-BRCA1/2 families in the Dutch population.

International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

“…31 Germline mutations have been detected in up to 3% of patients with familial PC. [31][32][33][34][35] The magnitude of PC risk in PALB2 mutation carriers has not been established. However, given the function of the PALB2 gene, the risk of PC among PALB2 gene mutation carriers is estimated to be similar to that found for BRCA2 gene mutation carriers.…”

Analysis of PALB2 Gene in BRCA1/BRCA2 Negative Spanish Hereditary Breast/Ovarian Cancer Families with Pancreatic Cancer Cases

“…Considering these two PALB2 variants as causal mutations, the prevalence of PALB2 mutation in our BRCA1/BRCA2 breast and pancreatic cancer series is 1.5% (2/132). Previous studies of breast/pancreatic cancer families have described prevalences from 0% (77 families analysed in Stadler et al [26], 45 in Adank et al [27], 29 in Guiorzo et al [28] and 28 in Harinck et al [29]), 2.1% (Hofstatter et al [24], 2 mutations in 94 families), to 4.8% (Peterlongo et al [20], 3 mutations in 62 families) reviewed in Table 4. Considering these studies with our data, the global prevalence of PALB2 mutation in breast/pancreatic cancer families is 1.5% (7 mutations in 467 families).…”

ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes

“…In attempts to discover the cause of their PC susceptibility, studies have been performed on familial FPC kindreds for known candidate genes that fall into two groups: (i) genes that cause inherited disorders that are associated with increased risk of PC development (e.g., BRCA1 , BRCA2 , and CDKN2A ) even in the absence of meeting criteria for these hereditary syndromes (279–281) and (ii) recently described genes such as palladin ( PALLD ) (282), ATM (283), and PALB2 (284,285) that were discovered by whole genome sequencing or linkage analysis of FPC kindred(s). As shown in Table 13 , results vary depending on the study population with mutations, for example, in BRCA1 ranging from 0 to 6% (281,286), BRCA2 ranging from 0 to 6% (281,287,288), CDKN2A ranging from 0 to 20% (280,281,288), and PALB2 ranging from 0 to 5% (281,285,288).…”