Elevated antibodies against Epstein–Barr virus among individuals predicted to carry nasopharyngeal carcinoma susceptibility variants
Coghill, Anna E. and Hsu, Wan-Lun and Yang, Qi and Wang, Cheng-Ping and Lou, Pei-Jen and Yu, Kelly J. and Yu, Guoqin and Diehl, Scott R. and Chen, Chien-Jen and Goldstein, Alisa M. and Hildesheim, Allan,, 99, 1268-1273 (2018),
doi = https://doi.org/10.1099/jgv.0.001115,
publicationName = Microbiology Society,
issn = 0022-1317,
abstract= 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.,
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