Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-Delta 32 mutation

Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the indust rialized world, but the environmental and genetic factors that contribute t o susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for in fection and progression to AIDS led us to examine a potential role of this gene in AIDS Lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-Delta 32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infectio n and progression toward AIDS. The CCR5 gene was not associated with a diff erence in risk for Kaposi's sarcoma, another common malignancy in AIDS pati ents, or opportunistic infections. Costimulation of normal phorbol 12-myris tate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proli ferative response, indicating that RANTES is a mitogen for B cells. Taken t ogether, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a d ecreased response of B cells to the mitogenic activity of RANTES.