Abstract
Simple SummaryHuman cytomegalovirus (HCMV) infects 40–70% of adult populations in developed countries and this is thought to be involved in breast cancer progression; however, reports of detection of the viral genome in breast tumors ranges from 0–100%. We optimized a method that is both sensitive and specific to detect HCMV DNA in tissues from Canadian breast cancer patients. Only ~42% of HCMV-seropositive patients expressed viral DNA in their breast tumors. Viral transcription was not detected in any HCMV-infected breast tumors, indicating a latent infection; however, HCMV seropositivity and the presence of latent infections in breast tumors were independently, and in combination, associated with increased metastasis. HCMV DNA-positive tumors were also associated with lower relapse-free survival. Therefore, HCMV infection status should be accounted for during the monitoring and treatment of breast cancer patients. Prevention or reducing the effects of HCMV infection could decrease morbidity and mortality from metastatic disease.Human cytomegalovirus (HCMV) infects 40–70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0–100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes. HCMV gB DNA was detected in 18.4% of 136 breast tumors while 62.8% of 94 breast cancer patients were seropositive for HCMV. mRNA for the HCMV immediate early gene was not detected in any sample, suggesting viral latency in breast tumors. HCMV seropositivity was positively correlated with age, body mass index and menopause. Patients who were HCMV seropositive or had HCMV DNA in their tumors were 5.61 (CI 1.77–15.67, p = 0.003) or 5.27 (CI 1.09–28.75, p = 0.039) times more likely to develop Stage IV metastatic tumors, respectively. Patients with HCMV DNA in tumors experienced reduced relapse-free survival (p = 0.042). Being both seropositive with HCMV DNA-positive tumors was associated with vascular involvement and metastasis. We conclude that determining the seropositivity for HCMV and detection of HCMV gB DNA in the breast tumors could identify breast cancer patients more likely to develop metastatic cancer and warrant special treatment.
Highlights
Breast cancer is the most common malignancy among women worldwide and it is their leading cause of death from cancer [1]
The LC-PCR analysis resulted in an estimate of 200 copies of the human cytomegalovirus (HCMV) viral genome in 10 μL of the original stock of HCMV DNA-positive control based on calculations using a previously established standard curve that was generated with purified HCMV DNA of known genome copies (Table 1) [62]; 104 copies of the viral genome were estimated to be present in 10 μL of the 1:10 diluted HCMV
We examined whether the presence of HCMV glycoprotein B (gB) DNA in breast tumors was associated with any patient characteristics
Summary
Breast cancer is the most common malignancy among women worldwide and it is their leading cause of death from cancer [1]. Examples of the risk factors for breast cancer development include aging, family history, genetic mutations, reproductive factors such as pregnancy and menopause, endogenous and exogenous effects of estrogen, unhealthy lifestyle such as drinking and smoking, high body-mass index and dense breast tissue [2,3,4,5,6]. Another potential risk factor for the development and progression of breast cancer is viral infection. The virus is found in cancerous tissues, including colorectal [15], prostate [16], ovarian [17] and glioblastoma cancers [18]
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