Clinical Relevance of +936 C>T VEGFA and c.233C>T bFGF Polymorphisms in Chronic Lymphocytic Leukemia.

Pilar Eroles,Eduardo Tormo,Begoña Pineda,Patricia Rodrigues,Sandra Ballester,María José Terol

doi:10.3390/genes11060686

Abstract

Angiogenesis process contributes to the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) being the levels of VEGFA and bFGF higher in patients than in healthy controls. Our aim was to evaluate the implication of angiogenesis factors genetic variants in the predisposition to B-CLL and their association with clinical factors and survival. We performed a population-based case-control study in 224 Spanish B-CLL patients and 476 healthy randomly selected controls to evaluate susceptibility to developing B-CLL. Six polymorphisms were evaluated: rs1109324, rs1547651, rs3025039 (+936 C>T), rs833052 of the VEGFA gene, rs1449683 (c.233C>T) of the bFGF gene and (−710 C>T) of the VEGFR1 gene. The association between clinical parameters and patient outcome was analyzed. Carriers of the CT/TT variants of rs3025039 showed a significant protective effect against developing B-CLL. The CT/TT variants of rs1449683 show a tendency towards the development of the disease and the same variants associated significantly with higher genetic risk and with reduced disease free survival. Moreover, the association persisted in the early-stage disease subgroup. Our study provides evidence of the protective effect of the T/- rs3025039 VEGFA variant against B-CLL development and the association of CT/TT variants of the rs1449683 bFGF gene with genetic risk and an adverse survival.

Highlights

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of mature monoclonal B cells in the blood, secondary lymphoid tissue and marrow [1,2]
Genotype frequencies of the single nucleotide polymorphism (SNP) evaluated in the VEGFA, VEGFR1 and bFGF genes were compared between 224 B-CLL cases and 476 healthy donors
The SNPs were successfully genotyped in more than 95% of the study samples and frequencies were adjusted for age and sex

Summary

Introduction

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of mature monoclonal B cells in the blood, secondary lymphoid tissue and marrow [1,2]. The incidence varies between geographical areas being the most common leukemia in the western world. Angiogenesis is an essential process in the development and growth of malignant tumors, and several studies indicate that it may be involved in the pathogenesis of B-CLL. This is a multistep process requiring integrated actions of a number of angiogenesis growth factors [4], among which the most potent inducers are the fibroblast growth factor (bFGF) and the vascular endothelial growth factor (VEGF) family [5,6,7].

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