Cytomegalovirus and Epstein-Barr virus in breast cancer.

Ann K Richardson,John D Potter,Trevor P Anderson,Bridget A Robinson,Helen Morrin,John F Pearson,Yen Phung,Logan C Walker,Margaret J Currie

doi:10.1371/journal.pone.0118989

Abstract

Findings of polymerase chain reaction (PCR) studies of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96%) were EBV IgG positive and 49 of 70 (70%) were CMV IgG positive. QPCR detected EBV in 24 (34%) of the tumour and 9 (13%) of the paired normal specimens and CMV in 0 (0%) of the tumour and 2 (3%) of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; ‘hit and run’ oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples.

Highlights

Breast cancer is the most commonly diagnosed cancer in women worldwide.[1]
Most tissue samples from wide-local excisions were unsuitable for obtaining paired samples because there was not enough normal tissue available that was >70mm from the tumour
The mean positivity for Epstein-Barr virus (EBV) is 26%, with 12 out of 54 (22.2%) studies across all assay types detecting positivity statistically indistinguishable from zero whereas only two (3.7%) studies are consistent with complete positivity

Summary

Introduction

Breast cancer is the most commonly diagnosed cancer in women worldwide.[1] Several human cancers can be caused by viruses and a virus, mouse mammary tumour virus (MMTV), causes breast cancer in mice.[2] We hypothesised that late exposure (in adulthood rather than in childhood) to a common virus such as CMV or EBV may cause breast cancer.[3, 4] Cytomegalovirus is ubiquitous in human populations but patterns of exposure differ among countries. Breast cancer incidence is low in those countries where most people seroconvert in childhood.

Methods

Results

Conclusion