Multiplex PCR/mass spectrometry screening of biological carcinogenic agents in human mammary tumors
Section snippets
Background
Breast cancer is the most common type of cancer in women worldwide, with an estimated 1.38 million new cases and over 450,000 deaths annually worldwide [1]. While 5–10% of breast cancer cases are caused by hereditary mutations [2], [3], the etiology of the majority of sporadic breast cancers remains enigmatic. Many studies have suggested a possible link between breast cancer pathogenesis and viral infection, particularly human papillomavirus (HPV), Epstein–Barr virus (EBV), simian virus 40
Objective
The objective of the present study was to explore the prevalence of 30 oncogenic HPVs, SV40, BKPyV, JCPyV, WUPyV, KIPyV, MCPyV, EBV and KSHV in tumor specimens from 100 breast cancer patients and 50 benign breast disease patients from Shaanxi Province of China using MS-HPV and MS-PEK.
Sample preparation
Sample sets were collected from 100 female breast cancer patients and 50 female benign breast disease patients who received surgery at the Department of Vascular and Endocrine Surgery, Xijing hospital, the Fourth Military Medical University, China, between October 2010 and October 2011. Exclusion criteria were systemic therapy prior to surgery, bilateral breast cancer, metastatic or recurrent disease, and cancer of other origin. Adjuvant therapy was based on current National Comprehensive
Sensitivity and specificity of the MS-PEK assay
The specificity of the MS-PEK method was analyzed using 1000 plasmids/reaction with specific inserts of each target virus. The results showed that this method accurately identified SV40, BKPyV, JCPyV, WUPyV, KIPyV, MCPyV, EBV and KSHV (data not shown). Using a standard 10-fold serial dilution of 1–10,000 plasmids/reaction, we determined that the detection limit per PCR reaction was approximately 10 copies (Fig. S1). Throughout the PCR-MS testing, there were no results from the negative
Discussion
In this study, we found that EBV was more prevalent among women with breast cancer than women with benign breast disease. Labrecque et al. detected EBV in 21% (19/91) samples from breast cancer patients using PCR targeting a region in the EBV BamHIW major repeat sequence [7]. In another study, Bonnet et al. detected EBV by PCR in 51% of the breast cancer specimens, while the virus was not detected in healthy tissue adjacent to the tumor. The presence of the EBV in breast cancers was confirmed
Funding
This work was supported by the Ministry of Science and Technology of the People's Republic of China (2011ZX10004-001), the National Natural Science Fund (81272899), Institute of Pathogen Biology, CAMS&PUMC (2013IPB102), the Shaanxi Fund (2013K12-03-03) and Xi’an Found (SF1323(3), the Discipline booster plan of Xi Jing Hospital (XJZT12Z07).
Competing interests
None declared.
Ethical approval
The study has been approved by the Xijing Hospital Ethics Committee. Written informed consent was obtained from each patient, the parents of the minors/children participants or blood donor volunteer.
References (36)
- et al.
Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women
Breast
(2007) - et al.
Viruses and human cancer: from detection to causality
Cancer Lett
(2011) - et al.
MCV and Merkel cell carcinoma: a molecular success story
Curr Opin Virol
(2012) - et al.
Sensitive and rapid detection of viruses associated with hand foot and mouth disease using multiplexed MALDI-TOF analysis
J Clin Virol
(2013) - et al.
Sequence analysis of Epstein–Barr virus EBNA-2 gene coding amino acid 148-487 in nasopharyngeal and gastric carcinomas
Virol J
(2012) - et al.
Possible role of EBV in breast cancer and other unusually EBV-associated cancers
Cancer Lett
(2011) - et al.
Lack of expression of the Epstein–Barr Virus (EBV) gene products, EBERs, EBNA1, LMP1, and LMP2A, in breast cancer cells
Lab Invest
(2002) - et al.
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Int J Cancer
(2010) - et al.
Hereditary breast cancer: new genetic developments, new therapeutic avenues
Hum Genet
(2008) - et al.
Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2
Science
(2003)
Evidence for a role of the Simian Virus 40 in human breast carcinomas
Breast Cancer Res Treat
The sero-epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in adults with cancer in Uganda
Int J Cancer
Human papilloma virus is associated with breast cancer
Br J Cancer
Epstein–Barr virus in epithelial cell tumors: a breast cancer study
Cancer Res
Viruses and human breast cancer
Future Microbiol
Role of viruses in the development of breast cancer
Infect Agent Cancer
Are viruses associated with human breast cancer? Scrutinizing the molecular evidence
Breast Cancer Res Treat
The possible involvement of virus in breast cancer
J Cancer Res Clin Oncol
Cited by (30)
Viral etiology involved in the emergence of the breast cancer
2019, Emerging and Reemerging Viral Pathogens: Volume 1: Fundamental and Basic Virology Aspects of Human, Animal and Plant PathogensIs human papillomavirus associated with breast cancer or papilloma presenting with pathologic nipple discharge?
2019, Cancer Treatment and Research CommunicationsEpstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation
2016, EBioMedicineCitation Excerpt :As exposure to virus frequently precedes the manifestation of cancer by years, and only a minority of individuals exposed to EBV will develop a related cancer, it is difficult to establish a causal role. An association of EBV infection with breast cancer has been reported from India (Joshi et al., 2009), China (Peng et al., 2014; He et al., 2012), Northern Africa (Fina et al., 2001; Hachana et al., 2011b) and southern Europe (Marrao et al., 2014; Mazouni et al., 2011; Labrecque et al., 1995). However, no mechanism of infection has been identified.
The prevalence of STL polyomavirus in stool samples from Chinese children
2015, Journal of Clinical VirologyCitation Excerpt :The frequent discovery of HPyVs in the gastrointestinal tract and stools suggests a potential involvement in gastroenteritis. Recently, we screened for viral DNA of the original ten HPyV species prior to the discovery of STLPyV, HPyV12 and NJPyV-2013, the HPyV species were isolated from stool samples [25] using MALDI-TOF mass spectrometry platform for multiplex PCR detection (mPCR-MS) [26–28]. It is the first report about the prevalence of ten HPyVs in stool samples from Chinese children [25].
An updated systemic review and meta-analysis on human papillomavirus in breast carcinogenesis
2023, Frontiers in Oncology
- 1
1These authors contributed equally.