Abstract
Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that recipient rs231775 genotype is significantly associated with tumorigenesis (P = 0.012). Multiplicative interaction between rs231775 AA and possible risk factors of malignancy revealed two significant results: rs231775 AA × primary diseases and rs231775 AA × number of HLA-mismatch. The frequency of haplotype TACAG was significantly higher in the tumor group (17.07%) than that in the nontumor group (1.53%). In addition, aristolochic acid nephropathy (P = 0.003) and the time of discovery of tumor (P = 0.000) also were independently associated with tumorigenesis. Our data show that the CTLA4 genotype rs231775 AA may be one of risk factors for the development of malignancy and haplotype TACAG was susceptible haplotype in Chinese kidney transplant recipients.
Highlights
Recipients with malignant tumors after renal transplantation are one of important factors affecting the long-term survival and are one of the first four most common causes of death following cardiovascular disease, infection, and liver failure [1]
Multivariate analyses revealed that age at time of transplant, gender, primary disease, pretransplant dialysis time, HLA-mismatch, renal transplantation, immunosuppressive regimen, blood transfusion, and acute rejection were not independent of tumor; the analyses showed that three risk factors, recipient rs231775 genotype (P = 0.012), aristolochic acid nephropathy (P = 0.003), and the time of discovery of tumor (P = 0.000), were independently associated with tumor (Supplementary Table 4)
The cytotoxic T lymphocyte-associated antigen 4 (CTLA4) single-nucleotide polymorphisms (SNPs) have been implicated in susceptibility to various cancers in different ethnic populations
Summary
Recipients with malignant tumors after renal transplantation are one of important factors affecting the long-term survival and are one of the first four most common causes of death following cardiovascular disease, infection, and liver failure [1]. Due to own humoral and cellular immune defects, there was high risk of malignancy in uremic patients. Kidney transplantation has become effective alternative treatment methods of uremia. The inventions of new immunosuppressive agents reduced the incidence of acute rejection and improved short-term graft survival rate, but long-term survival has not been significantly improved. A more direct role in the continuous advent of new immunosuppressive agents, kidney transplant short-term effect has been greatly improved, while, with the number of elderly patients receiving transplants increasing, the risk of cancer after transplantation will increase
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
