Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

Abstract : As both breast cancer incidence and the highly polymorphic genes for the human leukocyte antigen (HLA) component of the immune system differ across racial/ethnic groups, HLA may be a biologically based risk factor for breast cancer and explain some of its racial/ethnic variation. In a population-based series of 915 post-menopausal white, black and Hispanic breast cancer cases and controls, we determined HLA class I (A, B) and class II (DR, DO) genotypes through DNA methodology and calculated age- and risk4actor-adjusted odds ratios to estimate allele-specific risks. We found moderate associations of HLA alleles with breast cancer overall but varying with race/ethnicity. Overall, breast cancer risk was suggestively increased for allele A-33, suggestively decreased for alleles B-13 and B-39, and doubled for the DR-DO haplotype 0803. In whites, A-23 increased risk. In blacks, A-32, A-33 and DOB-5 increased risk, while DRB-9 reduced risk. In Hispanics, B-40 increased risk, while A-01, B-07, and B-45 decreased risk. Some associations were modified by disease stage at diagnosis, ER status of tumors, and breast cancer family history. Associations noted for A-01, A-23, A-32, B-07, DRB1-01, DOB1-02 and DOB1 -05 were consistent with observed racial/ethnic incidence differentials, but other associations were in contradictory directions. Our findings, limited by sample size and multiple comparisons, support a possible but complex role of HLA or linked loci in breast cancer occurrence and perhaps the racial/ethnic variation in its incidence.