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Dean, M. et al.

Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-delta32 mutation.

Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to 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 infection 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-delta32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi's sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, 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 decreased response of B cells to the mitogenic activity of RANTES.[1]

References

Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-delta32 mutation. Dean, M., Jacobson, L.P., McFarlane, G., Margolick, J.B., Jenkins, F.J., Howard, O.M., Dong, H.F., Goedert, J.J., Buchbinder, S., Gomperts, E., Vlahov, D., Oppenheim, J.J., O'Brien, S.J., Carrington, M. Cancer Res. (1999) [Pubmed]

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