Genetic Variants of NRAMP1 and Hepcidin (HAMP) in Cancer Patients Infected with Human Herpesvirus-6

Human herpesvirus-6 (HHV-6) is involved in immune modulation and contributes to cancer development through interactions with host genetic factors. Hepcidin (HAMP) and NRAMP1 genes play essential roles in iron metabolism and innate immunity, yet their polymorphisms remain poorly investigated in HHV-6-associated cancers. This study investigated the association between HAMP and NRAMP1 gene polymorphisms and HHV-6 infection in 40 confirmed HHV-6-positive cancer patients compared with 40 non-cancer, HHV-6-negative controls. Genomic DNA was extracted and verified by agarose gel electrophoresis. Hepcidin polymorphisms were analyzed using Tetra-ARMS PCR, while NRAMP1 (3'UTR) polymorphism was detected by PCR-RFLP. Cancer patients exhibited wild-type, mutant, and heterozygous hepcidin genotypes, whereas controls predominantly showed the wild-type genotype. Although allele frequency analysis revealed no statistically significant difference for the G and TG⁺ alleles between groups (p = 0.23), the hepcidin A allele (521 bp) was more frequent among cancer patients, suggesting a possible association with increased cancer susceptibility (odds ratio = 2.111). For NRAMP1, three genotypic patterns were identified (TG-/TG-, TG+/TG+, and TG-/TG+), and while no significant between-group difference was detected (p = 0.23), the TG+ allele demonstrated a potential two-fold increased cancer risk among carriers. These findings suggest that specific allelic variants-particularly the hepcidin A allele and NRAMP1 TG+ allele-may contribute to cancer susceptibility in HHV-6-infected individuals, highlighting a possible genetic-viral interaction that influences immune and iron-regulatory pathways in cancer development.