Genetic markers of immunoglobulin G and susceptibility to breast cancer.

Immunoglobulin GM allotypes, antigenic determinants of γ chains, are encoded by three very closely linked codominant genes on chromosome 14q32. Particular GM alleles/haplotypes are associated with antibody responses to certain tumor antigens and contribute to the cytotoxicity of breast cancer cells, but their possible role in susceptibility to this malignancy has not been adequately examined. Using a matched case-control design, we genotyped a large (1710 subjects) study population from Japan and Brazil for several GM alleles to determine whether these determinants are associated with susceptibility to breast cancer. After adjusting for the potential confounders, the GM 3 allele of IgG1 was significantly associated with susceptibility to breast cancer in white subjects from Brazil (OR=2.07, CI 1.16-3.71; p=0.0147). These data show that Caucasians with the GM 3 allele are over twice as likely to develop breast cancer as those who lack this allele. Since this allele modulates an immune evasion strategy of cytomegalovirus, the results also shed light on the possible mechanism underlying the reported involvement of this virus in the etiology of breast cancer.