Sex differences, family history of cancer, association with peptides matching the human endogenous retrovirus genes, and survival

抄録

Introduction: The molecular basis of sex differences, family history (FH), and their roles in survival remain unclear.

Methods: All participants (n = 2,654) underwent human leukocyte antigen testing to confirm FH among first and second-degree relatives. A total of 2,640 participants were followed up for survival. Based on the Escape from X-Inactivated Tumor Suppressor hypothesis, we classified female and male patients into four FH groups and evaluated their associations with sex, FH, peptides matching the human endogenous retrovirus (HERV) genes, and survival.

Results: Female patients were more likely to have an FH than male patients. Additionally, patients with FH had a higher incidence of multiple malignancies than those without FH. In contrast, female patients exhibited better survival than male patients, and patients with FH had better survival outcomes compared to those without FH. When comparing the FH groups between parents and grandparents, we hypothesized that X-chromosome inactivation (XCI), X-chromosome reactivation, and loss of Y chromosome (LOY) occurred in parents and patients. Furthermore, peptides matching the HERV genes exhibited both inhibitory and stimulatory effects on survival. A significant diversity was observed in the correlations between sex differences, FH, peptides matching the HERV genes, and survival. Moreover, survival rates decreased with age, whereas the frequencies of XCI and LOY increased.

Conclusions: A better understanding of the biological association between sex differences and FH is essential for personalized treatment and the identification of new candidates for cancer treatment.