%0 Journal Article %A Coghill, Anna E. %A Hsu, Wan-Lun %A Yang, Qi %A Wang, Cheng-Ping %A Lou, Pei-Jen %A Yu, Kelly J. %A Yu, Guoqin %A Diehl, Scott R. %A Chen, Chien-Jen %A Goldstein, Alisa M. %A Hildesheim, Allan %T Elevated antibodies against Epstein–Barr virus among individuals predicted to carry nasopharyngeal carcinoma susceptibility variants %D 2018 %J Journal of General Virology, %V 99 %N 9 %P 1268-1273 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.001115 %K NPC %K NPC genetics %K anti-EBV antibodies %K EBV-related cancer %I Microbiology Society, %X Epstein–Barr virus (EBV) is an obligatory factor in the development of nasopharyngeal carcinoma (NPC), and anti-EBV IgA antibodies are elevated many years prior to the development of NPC. Nearly all adults are infected with EBV, but only a few develop cancer, suggesting that additional co-factors, including genetic susceptibility, must be required for the disease to manifest. Individuals were selected from the Taiwan Family Study, a cohort of 3389 individuals from NPC multiplex families. Primary analyses were conducted among 671 individuals from 69 pedigrees with the strongest family history of disease (>3 NPC-affected family members). The likelihood that a given family member carried a NPC susceptibility variant was estimated using Mendelian segregation rules, assuming a dominant mode of inheritance. We compared anti-EBV IgA antibody seropositivity between family members predicted to be carriers of NPC-linked genetic variants and those with a lower likelihood of carrying such variants. Obligate carriers of NPC susceptibility variants (100 % predicted probability of harbouring the genetic mutation) were nine-fold more likely to be anti-EBV IgA positive compared to family members predicted not to carry disease-causing variants (OR=9.2; P-trend<0.001). This elevated risk was confirmed in analyses restricted to both unaffected individuals and pedigrees with EBV-related pathway variants identified through exome sequencing. Our data indicate that family members who are more likely to carry NPC susceptibility variants are also more likely to be anti-EBNA1 IgA seropositive. Genetic susceptibility associated with control over this common herpes virus is likely a co-factor in determining which EBV-infected adults develop NPC. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001115