Absence of Association betweenCCR5rs333 Polymorphism and Childhood Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. Ordinarily, these cells express CCR5 chemokine receptor, which directs the immune response to a cellular pattern and is involved in cancer pathobiology. The genetic rs333 polymorphism of CCR5 (Δ32), results in a diminished receptor expression, thus leading to impaired cell trafficking. The objective of the present study was to investigate the effect of CCR5 chemokine receptor rs333 polymorphism in the pathogenesis of ALL. The genotype distribution was studied in 79 patients and compared with 80 control subjects, in a childhood population of Southern Brazil. Genotyping was performed using DNA samples amplified by polymerase chain reaction with sequence-specific primers (PCR-SSP). The homozygous (Δ32/Δ32) deletion was not observed in any subject involved in the study. Heterozygous genotype was not associated with ALL risk (OR 0.7%; 95% CI 0.21–2.32; P > 0.05), nor recurrence status of ALL (OR 0.86; 95% CI 0.13–5.48; P > 0.05). This work demonstrated, for the first time, no significant differences in the frequency of the CCR5/Δ32 genotype between ALL and control groups, indicating no effect of this genetic variant on the ALL susceptibility and recurrence risk.

CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population

“…The migration of regulatory immune cells to tumor sites can create an immunosuppressor environment proper for cancer development. Also, cancer cells can subvert the anti-tumor action of chemokine-ligand interactions (187)(188)(189)(190)(191). Of note, CD4+ T cells are important modulators of the immune response, acting as drivers for the action of effector cells.…”

“…In this sense, Vieira-Filho et al (191) found an association between the presence of the CCR5D32 allele and susceptibility to neuroblastoma (191). Lastly, Oliveira et al (187) investigated the role of the CCR5D32 variant in acute lymphoblastic leukemia, but no association was found between the variant and the disease development (187). In conclusion, the CCR5 has varied influences in different types of cancer.…”

The association between CCR5 Δ32 polymorphism and susceptibility to breast cancer

“…As a member of the CC chemokine receptor group, chemokine C-C motif receptor 5 (CCR5) can regulate the trafficking and effector functions of memory/effector T cells, macrophages, immature dendritic cells and natural killer cells [ 14 ]. This receptor binds to the chemokines MIP-1α (CCL3), MIP-1β (CCL4), and RANTES (CCL5), and exerts its functions through G protein [ 15 ]. In addition, CCR5 also plays a pivotal role in cancer progression via recruiting immune cells [ 16 ].…”