|Title||Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Shan 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|
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.
|Alternate Journal||Front Oncol|
|PubMed Central ID||PMC6915105|
|Grant List||T32 CA221709 / CA / NCI NIH HHS / United States|