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Microbiology and Immunology

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Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications.

TitleGenetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications.
Publication TypeJournal Article
Year of Publication2019
AuthorsShan J, Chouchane A, Mokrab Y, Saad M, Boujassoum S, Sayaman RW, Ziv E, Bouaouina N, Remadi Y, Gabbouj S, Roelands J, Ma X, Bedognetti D, Chouchane L
JournalFront Oncol
Volume9
Pagination1328
Date Published2019
ISSN2234-943X
Abstract

Triple-negative breast cancer (TNBC) accounts for ~15-20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to investigate the susceptibility and prognostic implications of genetic variation in CCL5 signaling genes in TNBC in the present study. We characterized variants in and that of six other CCL5 signaling genes () among 1,082 unrelated Tunisian subjects (544 BC patients, including 196 TNBC, and 538 healthy controls), assessed the association of the variants with BC-specific overall survival (OVS) and progression-free survival (PFS), and correlated CCL5 mRNA and serum levels with genotypes. We found a highly significant association between the genotype (OR = 5.14; = 0.004) and TNBC risk, and identified a significant association between the allele and decreased PFS in TNBC. A decreased risk of lymph node metastasis was associated with the allele, particularly in (OR = 0.47; = 0.001). variants ( and ) were linked to CCL5 serum and mRNA levels. In the TCGA TNBC/Basal-like cohort the allele was associated with a decreased OVS. High expression of in breast tumors was significantly associated with an increased OVS in all BC patients, but particularly in TNBC/Basal-like patients. In conclusion, genetic variation in CCL5 signaling genes may predict not only TNBC risk but also disease aggressiveness.

DOI10.3389/fonc.2019.01328
Alternate JournalFront Oncol
PubMed ID31921621
PubMed Central IDPMC6915105
Grant ListT32 CA221709 / CA / NCI NIH HHS / United States

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