Serum antibodies to Epstein-Barr virus (EBV) antigens can be used to predict the risk of nasopharyngeal carcinoma (NPC). To investigate whether EBV seropositivity rates were higher among healthy family members from multiplex and sporadic families with NPC (i.e., families with multiple or single cases) compared to the general population, a study was conducted on 2,665 unaffected individuals from 140 multiplex and 413 sporadic families. The titers of the IgA antibody to the EBV capsid antigen (VCA-IgA) were compared to those of 904 controls from the general population. The VCA-IgA titer was correlated among sibling pairs to a high significance in both family types (P < 0.0001 and P = 0.0005 for the multiplex and the sporadic families, respectively); parent-offspring pairs also showed significant correlation (P < 0.0001 and P = 0.0002, respectively); and spouse pairs were correlated, but at lower significance levels (P = 0.0790 and P = 0.0040, respectively). When compared to the controls, among first-degree relatives in the multiplex families, the age- and gender-adjusted odds ratio (OR) was 2.06 (95% confidence interval 1.56-2.71), 3.55 (2.24-5.64), and 2.25 (1.57-3.23) for siblings, parents, and children, respectively. In the sporadic families, the adjusted OR was 1.55 (1.21-2.00) and 2.08 (1.51-2.86) for siblings and parents, respectively. The adjusted P-value of spouses lost significance in the multiplex families, but remained significant in the sporadic families (P = 0.0146). In conclusion, EBV seropositivity rates were elevated among unaffected family members in both multiplex and sporadic families with NPC.
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