Association of HLA-A, B, and C alleles and cancer susceptibility in 179 solid malignancies.

BACKGROUND

The major histocompatibility complex (MHC) genes are known to be capable of influencing the susceptibility of many cancers. All mammalian cells, including cancer cells, express MHC class I molecules consisting of human leukocyte antigens (HLA) A, B, and C. The tumor susceptibility of HLA-A, B, and C alleles has not been studied extensively in solid tumors.

METHODS

HLA-A, B, and C genotypes of 179 solid tumors were collected from Caris Comprehensive Tumor Profiling reports, including 45 GU, 44 GI, 28 pancreaticobiliary, 21 thoracic, 15 breast, 13 Gyn, among others. The tumors were mainly from Caucasians (82%). The HLA allele frequencies in the tumors were compared to those of respective ethnic populations in the US National Marrow Donor Program (NMDP) database. Fisher's exact tests were performed, adjusted values were calculated using Benjamini-Hochberg's method for false discovery rate (FDR), and Prevalence ratios (PRs) were calculated to quantify associations.

RESULTS

Twenty-one alleles were not listed in the NMDP. Among them, A11:303 alone was present in 11 carcinomas, and B08:222 was seen in 4 tumors. Among the alleles listed in the NMDP, C08:02, B14:02, A03:02, and B44:06 were significantly associated with tumors in Caucasian Americans (PR: 2.50-170), while B*44:02 appeared protective (PR: 0.36). Alleles with less significant associations were listed.

CONCLUSIONS

From the HLA-A, B, and C data of the 179 tumors, we identified several susceptible alleles and one protective allele. Of interest, 21 alleles were not listed in the NMDP. The limited cases prevented our analysis from identifying cancer-susceptible alleles in other races.