Allan Hildesheim (National Cancer Institute, NIH, USA)
“Use of Viral and Genetic Markers for Risk Stratification for Development of Screening Programs for the Early Detection of NPC”
- 1987 Use of viral and genetic markers for NPC risk stratification.
- 16% cancers are caused by infectious agents (Lancet Oncol 2012, de Martel)
- EBV vaccination: EBV gp350 (Coghill et al., Clin Cancer Res, 2016 High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma)
- Screening for NPC: (Chien et al., N Engl J Med, 2001 Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men)
- Individuals positive for anti-VCA IgA or anti-EBV DNase antibodies have a much higher risk for NPC (Yu et al., Clin Cancer Res, 2011 Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families.)
- For those unaffected families (members from NPC multiplex families) anti-EBV IgA-VCA and IgA-EBNA1 are the best (Hildesheim, Am J Epidemiol, 2013 Invited commentary: Epstein-Barr virus-based screening for the early detection of nasopharyngeal carcinoma: a new frontier)
- Protein array (EBV1 chip Muta, B95-8, Akata strains, Middledorf), Cohort design: NPC array project strategy. Screen for promising candidate markers using case-control design → evaluate top hits in population-based screening
- Special notes for case-control design: estimate sensitivity and specificity, but not positivity and negativity
- LF2 (IgG), BGLF2(IgG), Rta(IgG), BMRF1-EAD(IgA), BXLF1-TK(IgA) | two or three of them achieve highest SE and SP
- EBV DNA viral load in plasma (insensitive for early stage NPC)
- EBV DNA in nasopharynx swab (high specificity and sensitivity, combined with miRNA and DNA variants)
- Host genetic risk factors: only ~7–9 % NPC is familial, which has 5-10 fold increased risk
- Also comments on EBV lytic cycle replication in differentiated
有人踢館: 一方面anti-VCA是NPC高危險群，一方面說病人體內有anti-VCA似可neuturalize病毒、降低罹患NPC風險 這… Allan: OOXXOOXXOOXX
From Ming-Han
- Martel; lacent oncol 2012: each pathogen and cancer: good reference!!
- EBV Vaccine (gp350 vaccine) against NPC?
- Yes this antibody can block clinical diseases of IM but not infection?
- Vaccine and childhood?
- Some data said might be work for treatment of NPC?
- The facts:
- People with NPC have higher level ab against VCA and DNase; and vice versa.
- People with NPC with much lower ab against gp350 “at the time they have NPC”; and without NPC people with high level ab against gp350. (level of anti-gp350 study not like VCA and DNase have long-term predictable results).
- If people/patient have high level anti-VCA anti DNase ab; will also have high level anti-EBNA1 abs. (Yu, Taiwan group).
- @EBV protein microarray (sensitivity; specificity problem…? It seems he has a special but correct way to determine that).
- -Use patient’s serum to the microarray that had been coated with different EBV proteins to detect the antibody level.
Results:
High level of IgA against EBV-> associated to NPC
High level of IgG against EBV-> associated to lymphoma.
Top markers of antibodies in NPC high-risk or NPC patients: (all IgA)
LF2,
BGLF2,
BRLF1
BMRF1
BXLF1 (TK).
Now applying this array to BL, NKT, EBVaGC…etc.
In Aug EBV Meeting Session 10: Nasopharyngeal carcinoma and other epithelial cell tumors
Whole Exome Sequencing of NPC Multiplex Families Identifies Variants potentially Involved in EBV Control
Allan Hildesheim, National Cancer Institute, Rockville, USA