Suggestive evidence that Fc variants of IgG2 and FcγRIIa loci interact to contribute to the risk of prostate cancer.

GM and KM allotypes-hereditary antigenic variants of immunoglobulin γ and κ chains, respectively-and the genetic variants of activating Fcγ receptors (FcγR) are associated with the immunobiology of several malignant diseases, but their role in susceptibility to prostate cancer has not been examined. This investigation aimed to determine whether these genes-individually or in particular epistatic combinations-contribute to the risk of prostate cancer. We genotyped DNA from 200 Caucasian patients with prostate cancer and 185 healthy controls (matched for age, race, gender, and geography) for several GM, KM, FcγRIIa, and FcγRIIIa alleles by molecular methods. None of the genotypes by itself was associated with the risk of prostate cancer. However, particular alleles at GM 23 and FcγRIIa loci interactively contributed to the risk of this malignancy (p = 0.031), the odds ratios ranging from 0.44 in subjects homozygous for the GM 23- allele at the IgG2 locus and for the histidine allele at the FcγRIIa locus to 2.86 in subjects homozygous for the GM 23+ allele at the IgG2 locus and the histidine allele at the FcγRIIa locus. To our knowledge, this is the first report implicating GM and FcγR loci as risk/protective factors for prostate cancer. Additional, independent, studies are warranted to confirm and extend these findings.