Understanding Genetic Variations Associated with Familial Breast Cancer

Overview

Journal World J Surg Oncol

Publisher Biomed Central

Specialties General Surgery
Oncology

Date 2024 Oct 10

PMID 39390525

Authors

Manjusha Pal

Doutrina Das

Manoj Pandey

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is the most frequent cancer among women. Genetics are the main risk factor for breast cancer. Statistics show that 15-25% of breast cancers are inherited among those with cancer-prone relatives. BRCA1, BRCA2, TP53, CDH1, PTEN, and STK11 are the most frequent genes for familial breast cancer, which occurs 80% of the time. In rare situations, moderate-penetrance gene mutations such CHEK2, BRIP1, ATM, and PALB2 contribute 2-3%.

Methods: A search of the PubMed database was carried out spanning from 2005 to July 2024, yielding a total of 768 articles that delve into the realm of familial breast cancer, concerning genes and genetic syndromes. After exclusion 150 articles were included in the final review.

Results: We report on a set of 20 familial breast cancer -associated genes into high, moderate, and low penetrance levels. Additionally, 10 genetic disorders were found to be linked with familial breast cancer.

Conclusion: Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered.

Citing Articles

Development of a prognostic model based on the ceRNA network in Triple-Negative Breast cancer.

Zhu Y, Wang J, Xu B PeerJ. 2025; 13:e19063.

PMID: 40034665 PMC: 11874946. DOI: 10.7717/peerj.19063.

References

Akhter N, Dar S, Chattopadhyay S, Haque S, Anwer R, Wahid M . Impact of p53 arg72pro SNP on Breast Cancer Risk in North Indian Population. Curr Genomics. 2018; 19(5):395-410. PMC: 6030857. DOI: 10.2174/1389202919666171205104137. View

Parvani J, Taylor M, Schiemann W . Noncanonical TGF-β signaling during mammary tumorigenesis. J Mammary Gland Biol Neoplasia. 2011; 16(2):127-46. PMC: 3723114. DOI: 10.1007/s10911-011-9207-3. View

Zhang J, Sun J, Chen J, Yao L, Ouyang T, Li J . Comprehensive analysis of BRCA1 and BRCA2 germline mutations in a large cohort of 5931 Chinese women with breast cancer. Breast Cancer Res Treat. 2016; 158(3):455-62. DOI: 10.1007/s10549-016-3902-0. View

Gorodnova T, Kuligina E, Yanus G, Katanugina A, Abysheva S, Togo A . Distribution of FGFR2, TNRC9, MAP3K1, LSP1, and 8q24 alleles in genetically enriched breast cancer patients versus elderly tumor-free women. Cancer Genet Cytogenet. 2010; 199(1):69-72. DOI: 10.1016/j.cancergencyto.2010.01.020. View

Zemankova P, cerna M, Horackova K, Ernst C, Soukupova J, Borecka M . A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition. Breast. 2024; 75:103721. PMC: 10998186. DOI: 10.1016/j.breast.2024.103721. View

Valentini V, Bucalo A, Conti G, Celli L, Porzio V, Capalbo C . Gender-Specific Genetic Predisposition to Breast Cancer: Genes and Beyond. Cancers (Basel). 2024; 16(3). PMC: 10854694. DOI: 10.3390/cancers16030579. View

Garcia-Closas M, Chanock S . Genetic susceptibility loci for breast cancer by estrogen receptor status. Clin Cancer Res. 2008; 14(24):8000-9. PMC: 2668137. DOI: 10.1158/1078-0432.CCR-08-0975. View

Tajbakhsh A, Afzal Javan F, Rivandi M, Moezzi A, Abedini S, Asghari M . Significant association of TOX3/LOC643714 locus-rs3803662 and breast cancer risk in a cohort of Iranian population. Mol Biol Rep. 2018; 46(1):805-811. DOI: 10.1007/s11033-018-4535-7. View

Arnon J, Zick A, Maoz M, Salaymeh N, Gugenheim A, Marouani M . Clinical and genetic characteristics of carriers of the TP53 c.541C > T, p.Arg181Cys pathogenic variant causing hereditary cancer in patients of Arab-Muslim descent. Fam Cancer. 2024; 23(4):531-542. PMC: 11512851. DOI: 10.1007/s10689-024-00391-2. View

10.

Wesche J, Haglund K, Haugsten E . Fibroblast growth factors and their receptors in cancer. Biochem J. 2011; 437(2):199-213. DOI: 10.1042/BJ20101603. View

11.

Chatterjee G, Jimenez-Sainz J, Presti T, Nguyen T, Jensen R . Distinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity. Nucleic Acids Res. 2016; 44(11):5256-70. PMC: 4914107. DOI: 10.1093/nar/gkw242. View

12.

Shah N, Shah P, Panchal Y, Katudia K, Khatri N, Ray H . Mutation analysis of BRCA1/2 mutations with special reference to polymorphic SNPs in Indian breast cancer patients. Appl Clin Genet. 2018; 11:59-67. PMC: 5953318. DOI: 10.2147/TACG.S155955. View

13.

Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R . Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet. 2006; 38(11):1239-41. DOI: 10.1038/ng1902. View

14.

van der Post R, Vogelaar I, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N . Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015; 52(6):361-74. PMC: 4453626. DOI: 10.1136/jmedgenet-2015-103094. View

15.

Meyer K, Maia A, OReilly M, Teschendorff A, Chin S, Caldas C . Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol. 2008; 6(5):e108. PMC: 2365982. DOI: 10.1371/journal.pbio.0060108. View

16.

Lima E, Soares I, Danilovic D, Marui S . New mutation in the PTEN gene in a Brazilian patient with Cowden's syndrome. Arq Bras Endocrinol Metabol. 2013; 56(8):592-6. DOI: 10.1590/s0004-27302012000800022. View

17.

Graffeo R, Rana H, Conforti F, Bonanni B, Cardoso M, Paluch-Shimon S . Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D. Breast. 2022; 65:32-40. PMC: 9253488. DOI: 10.1016/j.breast.2022.06.003. View

18.

Walsh T, Casadei S, Coats K, Swisher E, Stray S, Higgins J . Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006; 295(12):1379-88. DOI: 10.1001/jama.295.12.1379. View

19.

Filippini S, Vega A . Breast cancer genes: beyond BRCA1 and BRCA2. Front Biosci (Landmark Ed). 2013; 18(4):1358-72. DOI: 10.2741/4185. View

20.

Tedaldi G, Tebaldi M, Zampiga V, Danesi R, Arcangeli V, Ravegnani M . Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer. Oncotarget. 2017; 8(29):47064-47075. PMC: 5564544. DOI: 10.18632/oncotarget.16791. View