Human Leukocyte Antigen-G Polymorphisms Association With Cancer Post-Heart Transplantation

Abstract

Background: Post transplantation, a major complication is the development of malignancies. Human Leukocyte Antigen (HLA)-G is a molecule that inhibits the immune system and it is utilized by malignant cells to hide from the immune system. Expression of HLA-G from the donor and recipient cells in transplant patients is regulated by gene variations however, the association between genotype and cancer remains unknown. Our objective was to determine the association between genotype and outcome.

Methods: Heart transplant recipients (251) and available corresponding donors (196) samples were genotyped for polymorphisms and the association of polymorphisms to outcome was evaluated with parametric hazard regression models.

Results: Risk of cancer was 22% at 10years post-transplantation. The mean follow-up was of 4.9±3.6years. In a multivariable analysis, donor-recipient SNP 3187 matching was identified as a protective factor for cancer (hazard ratio 0.43; 95% confidence interval 0.19-0.93; p=0.03). While coding region allele (haplotype 6) was identified as an independent risk factor (hazard ratio 3.7; 95% confidence interval 1.36-10.06; p=0.01).

Conclusion: In this investigation, we identified an association between cancer post-transplantation and HLA-G polymorphisms, which may reveal a pathway for potential diagnostic and therapeutic strategies for cancer post-transplantation.

Keywords: Cancer; HLA-G; HLA-G polymorphisms; Post-heart transplantation.