Double Heterozygosity for Germline Mutations in Chinese Breast Cancer Patients

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jul 27

PMID 39061189

Authors

Ava Kwong

Cecilia Y S Ho

Chun-Hang Au

Edmond S K Ma

Affiliations

Soon will be listed here.

Abstract

Double pathogenic mutations occurring in an individual are considered a rare event. The introduction of a multiple-gene panel at Hong Kong Hereditary Breast Cancer Family Registry has allowed the identification of pathogenic variants in multiple genes, providing more information on clinical management and surveillance to the proband and their family members. Breast cancer patients who are double heterozygous (DH) for different hereditary breast and ovarian cancer syndrome (HBCO)-related genes were identified from a cohort of 3649 Chinese patients. Nine patients (0.25%) were observed to have germline DH mutations in , , , , , , , , and . Three probands were diagnosed with unilateral breast cancer, two patients were diagnosed with bilateral breast cancer, and four patients had multiple primary cancers. The median age for breast cancer diagnosis was an early age of 36 years. Chinese DH carriers did not show worse phenotypes or have a significantly downhill clinical presentation. However, seven out of nine (77.8%) of our DH carriers harbored a mutation, and four of them (44.4%) developed bilateral breast cancer, suggesting Chinese DH individuals may have a higher chance of having bilateral breast cancer than other populations ( = 0.0237).

Citing Articles

Understanding genetic variations associated with familial breast cancer.

Pal M, Das D, Pandey M World J Surg Oncol. 2024; 22(1):271.

PMID: 39390525 PMC: 11465949. DOI: 10.1186/s12957-024-03553-9.

References

Meynard G, Mansi L, Lebahar P, Villanueva C, Klajer E, Calcagno F . First description of a double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient: A case report. Oncol Rep. 2017; 37(3):1573-1578. DOI: 10.3892/or.2017.5422. View

Sokolenko A, Bogdanova N, Kluzniak W, Preobrazhenskaya E, Kuligina E, Iyevleva A . Double heterozygotes among breast cancer patients analyzed for BRCA1, CHEK2, ATM, NBN/NBS1, and BLM germ-line mutations. Breast Cancer Res Treat. 2014; 145(2):553-62. DOI: 10.1007/s10549-014-2971-1. View

Nomizu T, Matsuzaki M, Katagata N, Kobayashi Y, Sakuma T, Monma T . A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes. Breast Cancer. 2012; 22(5):557-61. DOI: 10.1007/s12282-012-0432-4. View

Cote S, Arcand S, Royer R, Nolet S, Mes-Masson A, Ghadirian P . The BRCA2 c.9004G>A (E2002K) [corrected] variant is likely pathogenic and recurs in breast and/or ovarian cancer families of French Canadian descent. Breast Cancer Res Treat. 2011; 131(1):333-40. DOI: 10.1007/s10549-011-1796-4. View

Frank T, Deffenbaugh A, Reid J, Hulick M, Ward B, Lingenfelter B . Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002; 20(6):1480-90. DOI: 10.1200/JCO.2002.20.6.1480. View

Vietri M, Caliendo G, DElia G, Resse M, Casamassimi A, Minucci P . Five Italian Families with Two Mutations in Genes. Genes (Basel). 2020; 11(12). PMC: 7761639. DOI: 10.3390/genes11121451. View

Le Page C, Rahimi K, Rodrigues M, Heinzelmann-Schwarz V, Recio N, Tommasi S . Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis. Gynecol Oncol. 2019; 156(2):377-386. DOI: 10.1016/j.ygyno.2019.11.019. View

Bogdanova N, Antonenkova N, Rogov Y, Karstens J, Hillemanns P, Dork T . High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Clin Genet. 2010; 78(4):364-72. DOI: 10.1111/j.1399-0004.2010.01473.x. View

Sokolenko A, Iyevleva A, Mitiushkina N, Suspitsin E, Preobrazhenskaya E, Kuligina E . Hereditary breast-ovarian cancer syndrome in Russia. Acta Naturae. 2012; 2(4):31-5. PMC: 3347586. View

10.

Pilato B, De Summa S, Danza K, Lambo R, Angelo Paradiso , Tommasi S . Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report. Breast Cancer Res Treat. 2010; 124(3):875-8. DOI: 10.1007/s10549-010-1125-3. View

11.

Friedman E, Bruchim R, Kruglikova A, Risel S, Levy-Lahad E, Halle D . Double heterozygotes for the Ashkenazi founder mutations in BRCA1 and BRCA2 genes. Am J Hum Genet. 1998; 63(4):1224-7. PMC: 1377473. DOI: 10.1086/302040. View

12.

Neben C, Zimmer A, Stedden W, van den Akker J, OConnor R, Chan R . Multi-Gene Panel Testing of 23,179 Individuals for Hereditary Cancer Risk Identifies Pathogenic Variant Carriers Missed by Current Genetic Testing Guidelines. J Mol Diagn. 2019; 21(4):646-657. DOI: 10.1016/j.jmoldx.2019.03.001. View

13.

Leegte B, van der Hout A, Deffenbaugh A, Bakker M, Mulder I, ten Berge A . Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline mutations. J Med Genet. 2005; 42(3):e20. PMC: 1736012. DOI: 10.1136/jmg.2004.027243. View

14.

Keupp K, Hampp S, Hubbel A, Maringa M, Kostezka S, Rhiem K . Biallelic germline BRCA1 mutations in a patient with early onset breast cancer, mild Fanconi anemia-like phenotype, and no chromosome fragility. Mol Genet Genomic Med. 2019; 7(9):e863. PMC: 6732317. DOI: 10.1002/mgg3.863. View

15.

Tai Y, Domchek S, Parmigiani G, Chen S . Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007; 99(23):1811-4. PMC: 2267289. DOI: 10.1093/jnci/djm203. View

16.

Rebbeck T, Friebel T, Mitra N, Wan F, Chen S, Andrulis I . Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women. Breast Cancer Res. 2016; 18(1):112. PMC: 5106833. DOI: 10.1186/s13058-016-0768-3. View

17.

Turnbull C, Seal S, Renwick A, Warren-Perry M, Hughes D, Elliott A . Gene-gene interactions in breast cancer susceptibility. Hum Mol Genet. 2011; 21(4):958-62. PMC: 4125627. DOI: 10.1093/hmg/ddr525. View

18.

Randall T, Bell K, Rebane B, Rubin S, Boyd J . Germline mutations of the BRCA1 and BRCA2 genes in a breast and ovarian cancer patient. Gynecol Oncol. 1998; 70(3):432-4. DOI: 10.1006/gyno.1998.5081. View

19.

Zuradelli M, Peissel B, Manoukian S, Zaffaroni D, Barile M, Pensotti V . Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics. Breast Cancer Res Treat. 2010; 124(1):251-8. DOI: 10.1007/s10549-010-0853-8. View

20.

Chen S, Iversen E, Friebel T, Finkelstein D, Weber B, Eisen A . Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006; 24(6):863-71. PMC: 2323978. DOI: 10.1200/JCO.2005.03.6772. View