title: CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients.
abstract: The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.
authors: Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, PR, Brazil.
authors: Karen Brajão
authors: KB
authors: de Oliveira
authors: Roberta Losi
authors: RL
authors: Guembarovski
authors: Julie Massayo Maeda
authors: JM
authors: Oda
authors: Mário Sérgio
authors: MS
authors: Mantovani
authors: Clisia Mara
authors: CM
authors: Carrera
authors: Edna Maria Vissoci
authors: EM
authors: Reiche
authors: Julio Cesar
authors: JC
authors: Voltarelli
authors: Ana Cristina
authors: AC
authors: da Silva do Amaral Herrera
authors: Maria Angelica Ehara
authors: MA
authors: Watanabe