Coghill A.EHsu W.-LYang QCHENG-PING WANGPEI-JEN LOUYu K.JYu GDiehl S.RChen C.-JGoldstein A.MHildesheim A.2020-10-272020-10-2720180022-1317https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052991736&doi=10.1099%2fjgv.0.001115&partnerID=40&md5=5305e28d91039f3cafd68ace0487dc67https://scholars.lib.ntu.edu.tw/handle/123456789/518188Epstein–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. ? 2018 The Authors.[SDGs]SDG3immunoglobulin A antibody; immunoglobulin A; virus antibody; Article; cohort analysis; Epstein Barr virus; family history; gene mutation; genetic linkage; genetic susceptibility; genetic variability; heterozygote; human; major clinical study; nasopharynx carcinoma; nonhuman; pedigree; predictive value; priority journal; risk assessment; Taiwan; whole exome sequencing; blood; carcinoma; Epstein Barr virus; female; genetic predisposition; genetic variation; genetics; male; nasopharynx tumor; virology; Antibodies, Viral; Carcinoma; Female; Genetic Predisposition to Disease; Genetic Variation; Herpesvirus 4, Human; Humans; Immunoglobulin A; Male; Nasopharyngeal Neoplasmsjournal article10.1099/jgv.0.001115299751842-s2.0-85052991736