Chemokine and Chemokine Receptor Gene Variants and Risk of Non-Hodgkin’s Lymphoma in Human Immunodeficiency Virus-1–Infected Individuals

Abstract

Normal B-lymphocyte maturation and proliferation are regulated by chemotactic cytokines (chemokines), and genetic polymorphisms in chemokines and chemokine receptors modify progression of human immunodeficiency virus-1 (HIV-1) infection. Therefore, 746 HIV-1–infected persons were examined for associations of previously described stromal cell-derived factor 1 (SDF-1) chemokine and CCR5 and CCR2 chemokine receptor gene variants with the risk of B-cell non-Hodgkin’s lymphoma (NHL). The SDF1-3′A chemokine variant, which is carried by 37% of whites and 11% of blacks, was associated with approximate doubling of the NHL risk in heterozygotes and roughly a fourfold increase in homozygotes. After a median follow-up of 11.7 years, NHL developed in 6 (19%) of 30 SDF1-3′A/3′A homozygotes and 22 (10%) of 202 SDF1-+/3′A heterozygotes, compared with 24 (5%) of 514 wild-type subjects. The acquired immunodeficiency syndrome (AIDS)-protective chemokine receptor variant CCR5-▵32 was highly protective against NHL, whereas the AIDS-protective variant CCR2-64I had no significant effect. Racial differences in SDF1-3′A frequency may contribute to the lower risk of HIV-1–associated NHL in blacks compared with whites. SDF-1 genotyping of HIV-1–infected patients may identify subgroups warranting enhanced monitoring and targeted interventions to reduce the risk of NHL.