Risk factors for Epstein Barr virus-associated cancers: a systematic review, critical appraisal, and mapping of the epidemiological evidence
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background Epstein Barr Virus (EBV) infects 90%-95% of all adults globally and causes~1% of all cancers. Differing proportions of Burkitt’s lymphoma (BL), gastric carcinoma (GC), Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC) are associated with EBV. We sought to
systematically review the global epidemiological evidence for risk factors
that (in addition to EBV) contribute to the development of the EBV-associated forms of these cancers, assess the quality of the evidence, and
compare and contrast the cancers.
Methods MEDLINE, Embase and Web of Science were searched for studies of risk factors for EBV-associated BL, GC, HL and NPC without language or temporal restrictions. Studies were excluded if there was no
cancer-free comparator group or where analyses of risk factors were inadequately documented. After screening and reference list searching, data
were extracted into standardised spreadsheets and quality assessed. Due
to heterogeneity, a narrative synthesis was undertaken.
Results 9916 hits were retrieved. 271 papers were retained: two BL, 24
HL, one GC and 244 NPC. The majority of studies were from China,
North America and Western Europe. Risk factors were categorised as dietary, environmental/non-dietary, human genetic, and infection and clinical. Anti-EBV antibody load was associated with EBV-associated GC and
BL. Although the evidence could be inconsistent, HLA-A alleles, smoking, infectious mononucleosis and potentially other infections were risk
factors for EBV-associated HL. Rancid dairy products; anti-EBV antibody
and EBV DNA load; history of chronic ear, nose and/or throat conditions;
herbal medicine use; family history; and human genetics were risk factors
for NPC. Fresh fruit and vegetable and tea consumption may be protective against NPC.
Conclusions Many epidemiological studies of risk factors in addition to
EBV for the EBV-associated forms of BL, GC, HL and NPC have been undertaken, but there is a dearth of evidence for GC and BL. Available evidence is of variable quality. The aetiology of EBV-associated cancers likely results from a complex intersection of genetic, clinical, environmental
and dietary factors, which is difficult to assess with observational studies.
Large, carefully designed, studies need to be strategically undertaken to
harmonise and clarify the evidence.
Registration PROSPERO CRD42017059806
systematically review the global epidemiological evidence for risk factors
that (in addition to EBV) contribute to the development of the EBV-associated forms of these cancers, assess the quality of the evidence, and
compare and contrast the cancers.
Methods MEDLINE, Embase and Web of Science were searched for studies of risk factors for EBV-associated BL, GC, HL and NPC without language or temporal restrictions. Studies were excluded if there was no
cancer-free comparator group or where analyses of risk factors were inadequately documented. After screening and reference list searching, data
were extracted into standardised spreadsheets and quality assessed. Due
to heterogeneity, a narrative synthesis was undertaken.
Results 9916 hits were retrieved. 271 papers were retained: two BL, 24
HL, one GC and 244 NPC. The majority of studies were from China,
North America and Western Europe. Risk factors were categorised as dietary, environmental/non-dietary, human genetic, and infection and clinical. Anti-EBV antibody load was associated with EBV-associated GC and
BL. Although the evidence could be inconsistent, HLA-A alleles, smoking, infectious mononucleosis and potentially other infections were risk
factors for EBV-associated HL. Rancid dairy products; anti-EBV antibody
and EBV DNA load; history of chronic ear, nose and/or throat conditions;
herbal medicine use; family history; and human genetics were risk factors
for NPC. Fresh fruit and vegetable and tea consumption may be protective against NPC.
Conclusions Many epidemiological studies of risk factors in addition to
EBV for the EBV-associated forms of BL, GC, HL and NPC have been undertaken, but there is a dearth of evidence for GC and BL. Available evidence is of variable quality. The aetiology of EBV-associated cancers likely results from a complex intersection of genetic, clinical, environmental
and dietary factors, which is difficult to assess with observational studies.
Large, carefully designed, studies need to be strategically undertaken to
harmonise and clarify the evidence.
Registration PROSPERO CRD42017059806
Date Issued
2020-06
Date Acceptance
2020-01-01
Citation
Journal of Global Health, 2020, 10 (1), pp.1-4
ISSN
2047-2978
Publisher
International Global Health Society
Start Page
1
End Page
4
Journal / Book Title
Journal of Global Health
Volume
10
Issue
1
Copyright Statement
© 2020 The Author(s)
JoGH © 2020 ISoGH (https://creativecommons.org/licenses/by/4.0/legalcode).
JoGH © 2020 ISoGH (https://creativecommons.org/licenses/by/4.0/legalcode).
Sponsor
Wellcome Trust
Identifier
http://jogh.org/documents/issue202001/jogh-10-010405.pdf
Grant Number
536857
Subjects
1117 Public Health and Health Services
Publication Status
Published online
Date Publish Online
2020-01-01