Incidence of multiple primary malignancies, human leukocyte antigen-restricted human endogenous retrovirus gene-derived peptides, and survival

Abstract

Introduction: Some patients are more susceptible to multiple primary malignancies (MPMs). However, understanding of the effects of this susceptibility on the benefits and detriments to patient survival are poorly understood. Methods: Participants (n = 3,263) underwent human leukocyte antigen (HLA) testing, surgery, and histological confirmation, and were confirmed with the date of surgery or diagnosis of metachronous MPMs. Risk factors for MPM included sex, age, interval period between first primary malignancy and metachronous malignancy, treatment, family history, germ layer of tumor origin, and MPM-relevant HLA-restricted human endogenous retrovirus (HERV) gene-derived peptides, which were examined for their association with the incidence of MPMs and overall survival. Results: Patients susceptible to MPMs included those aged 60 years and over, those who underwent surgery only, those with non-endoderm-origin tumors, those with a family history of malignancies, and those in the survival-disadvantage peptide groups. Except for patients with esophageal MPM (+), patients with MPM (+) had poorer overall survival than those with MPM (-). Patients with esophageal MPM (+) had more survival-favorable peptides and fewer survival-unfavorable peptides. HLAs more susceptible to MPM included HLA-A2, -B7, -B13, -B39, -B55, -B62, -Cw6, and -Cw10, and those that were less susceptible to MPM included HLA-B56 and -Cw8. Patients who were MPM (+) with survival-favorable peptide groups B and H, and HLA-A2, -B61, -DQ4, or -DR15, had significantly better survival than patients without these peptides. Conclusion: MPM-relevant HLA-restricted human endogenous retrovirus gene-derived peptides associated with the incidence of MPMs and patients had differential effects on patient survival.