BRCA1 and BRCA2 are the most well-known genes associated with an increased risk for developing breast cancer. However, mutations of other genes, such as PALB2, TP53, ATM, BRIP1, CHEK2, CDH1, PTEN, and STK11, have also been associated with an increased risk for the disease.1,2
Recently, Tedaldi and colleagues conducted a next-generation sequencing analysis of 227 patients with initial breast cancer and 28 patients with initial ovarian cancer.3 Among 181 patients with no pathogenic mutations, there were more than 1000 gene variants, with an average of 6 variants per patient.
The researchers detected 81 pathogenic/likely pathogenic mutations in 74 of 255 (29%) patients in the study. Of these mutations, 32 (39.5%) were BRCA1, 26 (32.1%) were BRCA2, and 23 (28.4%) were other gene mutations.
A total of 13 patients had gene alterations in ATM, BRIP1, PALB2, PPM1D, and RAD51D, which have been associated with an increased risk for breast cancer. PALB2 was the third most frequent gene detected in the study population (after BRCA1 and BRCA2).3
In a separate study published in the New England Journal of Medicine, Antoniou and colleagues reported that PALB2 was the most important breast cancer predisposition gene after BRCA1 and BRCA2.4 There is also strong evidence that PALB2 and ATM are associated with increased breast cancer risk in European women.5
These new genetic markers may help to stratify risk in women with breast cancer and provide potential therapeutic targets for researchers.
1. Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int. 2013 Mar 21. Epub ahead of print.
2. Nielsen FC, van Overeem Hansen T, Sørensen CS. Hereditary breast and ovarian cancer: new genes in confined pathways. Nat Rev Cancer. 2016;16:599-612.
3. Tedaldi G, Tebaldi M, Zampiga V, et al. Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer. Oncotarget. 2017;8:47064-47075.
4. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497-506.
5. Southey MC, Goldgar DE, Winqvist R, et al. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS. J Med Genet. 2016;53:800-811.