Carcinogenic viruses and solid cancers without sufficient evidence of causal association

Paoli, Paolo De; Carbone, Antonino

doi:10.1002/ijc.27995

Cited by 41 publications

(35 citation statements)

References 120 publications

(268 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results indicate that despite the controversial DNA detection of human papillomavirus (54,55), it was not a problem for EBV DNA detection (13,17). The subgroup analysis by types of control tissue also showed the same findings.…”

Section: Discussionsupporting

confidence: 65%

“…Since the proposal of the association between breast cancer and EBV in 1995 by Labrecque et al (11), it has remained controversial to date (12). Incidentally, in order to meet the criteria required to demonstrate that a specific virus may cause cancer (13,14), a case-control study instead of a case study is required (15). However, tumorbased case-control study using cancer tissues has a drawback of making measurement errors (14,16).…”

Section: Contextmentioning

confidence: 99%

See 1 more Smart Citation

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Bae

Kim

2016

Arch Clin Infect Dis

View full text Add to dashboard Cite

Context: The association between 'Epstein-Barr' virus (EBV) and breast cancer risk still remains controversial. A Systemic Review (SR) published in 2012 reported that there might be a statistically significant association between EBV and risk of breast cancer. However, errors were found in the appraisal process of the concerned SR. Objectives:The aim of this report was to conduct an adaptive meta-analysis with additional extraction of relevant papers published up until September 2015.Data Sources: The lists of references, cited articles and related articles provided by PubMed were made using the articles selected in the previous SR.Study Selection: Among these articles, only case-control studies using Polymerase Chain Reaction (PCR) techniques to detect EBV DNA in tissues were selected. Data Extraction: The summary odds ratio (SOR) and the 95% confidence interval (CI) were calculated though meta-analysis.Results: A total of 20 case-control studies were selected, and the total numbers of subjects in the case and control groups were 1947 and 1010, respectively. The findings of this meta-analysis revealed that EBV infection might increase the risk of breast cancer (SOR = 3.84, 95% CI: 2.24-6.58; I-squared = 62.2%). Sub-group analyses by region, sample type, and control tissue showed that a statistical significance of the risk was still secured. Conclusions:The findings of the meta-epidemiological study support that EBV infection may increase the risk of breast cancer. Nested case-control studies are required in the future.

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Contextmentioning

confidence: 99%

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Bae

Kim

2016

Arch Clin Infect Dis

View full text Add to dashboard Cite

show abstract

“…In this study, we performed the systematic screening for potentially oncogenic viruses in nine cancer types from TCGA (Table 1), most of which were not previously known to be associated with viruses or have controversial reports in this regard [12,13]. After subtraction of non-viral sequences, unaligned fragments were used in virus identification (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data

Salyakina

Tsinoremas

2013

Hum Genomics

View full text Add to dashboard Cite

BackgroundUp to 20% of cancers worldwide are thought to be associated with microbial pathogens, including bacteria and viruses. The widely used methods of viral infection detection are usually limited to a few a priori suspected viruses in one cancer type. To our knowledge, there have not been many broad screening approaches to address this problem more comprehensively.MethodsIn this study, we performed a comprehensive screening for viruses in nine common cancers using a multistep computational approach. Tumor transcriptome and genome sequencing data were available from The Cancer Genome Atlas (TCGA). Nine hundred fifty eight primary tumors in nine common cancers with poor prognosis were screened against a non-redundant database of virus sequences. DNA sequences from normal matched tissue specimens were used as controls to test whether each virus is associated with tumors.ResultsWe identified human papilloma virus type 18 (HPV-18) and four human herpes viruses (HHV) types 4, 5, 6B, and 8, also known as EBV, CMV, roseola virus, and KSHV, in colon, rectal, and stomach adenocarcinomas. In total, 59% of screened gastrointestinal adenocarcinomas (GIA) were positive for at least one virus: 26% for EBV, 21% for CMV, 7% for HHV-6B, and 20% for HPV-18. Over 20% of tumors were co-infected with multiple viruses. Two viruses (EBV and CMV) were statistically significantly associated with colorectal cancers when compared to the matched healthy tissues from the same individuals (p = 0.02 and 0.03, respectively). HPV-18 was not detected in DNA, and thus, no association testing was possible. Nevertheless, HPV-18 expression patterns suggest viral integration in the host genome, consistent with the potentially oncogenic nature of HPV-18 in colorectal adenocarcinomas. The estimated counts of viral copies were below one per cell for all identified viruses and approached the detection limit.ConclusionsOur comprehensive screening for viruses in multiple cancer types using next-generation sequencing data clearly demonstrates the presence of viral sequences in GIA. EBV, CMV, and HPV-18 are potentially causal for GIA, although their oncogenic role is yet to be established.

show abstract

“…Because the SV40, JC and BK polyomaviruses induce tumors in animal models, it has been extensively investigated whether these viruses also contribute to human malignancy. However, only for MCPyV a causal relation with a human malignancy has been convincingly demonstrated …”

Section: Resultsmentioning

confidence: 99%

Characterization of functional domains in the Merkel cell polyoma virus Large T antigen

Houben

Angermeyer

Haferkamp

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Merkel cell polyomavirus (MCPyV)-positive Merkel cell carcinoma (MCC) tumor cell growth is dependent on the expression of a viral Large T antigen (LT) with an intact retinoblastoma protein (RB)-binding site. This RB-binding domain in MCPyV-LT is-in contrast to other polyomavirus LTs (e.g., SV40)-embedded between two large MCPyV unique regions (MUR1 and MUR2). To identify elements of the MCPyV-LT necessary for tumor cell growth, we analyzed the rescue activity of LT variants following knockdown of the endogenous LT in MCC cells. These experiments demonstrate that nuclear localization is essential for LT function, but that a motif previously described to be a nuclear localization sequence is neither required for nuclear accumulation of truncated MCPyV-LT nor for promotion of MCC cell proliferation. Furthermore, large parts of the MURs distal to the RB binding domain as well as ALTO-a second protein encoded by an alternative reading frame in the MCPyV-LT mRNA-are completely dispensable for MCPyV-driven tumor cell proliferation. Notably, even MCPyV-LTs in which the entire MURs have been removed are still able to promote MCC cellular growth although rescue activity is reduced which may be due to MUR1 being required for stable LT expression in MCC cells. Finally, we provide evidence implying that-while binding to Vam6p is not essential-HSC-70 interaction is significantly involved in mediating MCPyV-LT function in MCC cells including growth promotion and induction of E2F target genes.Polyomaviruses are small DNA viruses with a circular double-stranded genome coding for 5-9 proteins. 1 The genome is divided into an early and a late region. From the early region the T antigens (TA) are derived by differential splicing of a common transcript while the late region encodes for capsid proteins into which the viral genome is packaged. 2 It has long been known that polyomaviruses-as the name indicates-can induce tumor formation. 3 Until recently, however, this had only been observed in animal models whiledespite extensive research and controversial discussion-no convincing evidence for a contribution of the Simian Virus 40 (SV40), a monkey polyomavirus that is also present in the human population, or the two well-studied human polyomaviruses JC and BK to human malignancies could be obtained. 4,5 In contrast, one of the seven newly identified human polyomaviruses discovered during the last 6 years, the Merkel cell polyomavirus (MCPyV), is now well established as a causal factor of Merkel cell carcinoma (MCC). 2,4,6 MCC is a rare but very aggressive skin cancer with high mortality rates. Immunosuppression, UV exposure and old age are risk factors for developing MCC. 7 The molecular pathogenesis of MCC, however, remained enigmatic until MCPyV was discovered as monoclonally integrated into the genome of most MCCs indicating that integration occurred prior to clonal expansion of the tumor cells. 8 In many different countries the presence of MCPyV in the vast majority of MCC tumors has been confirmed, 9-12 and a recent publication s...

show abstract

Carcinogenic viruses and solid cancers without sufficient evidence of causal association

Cited by 41 publications

References 120 publications

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Epstein-Barr Virus Infection and Risk of Breast Cancer: An Adaptive Meta-Analysis for Case-Control Studies

Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data

Characterization of functional domains in the Merkel cell polyoma virus Large T antigen

Contact Info

Product

Resources

About