Abstract
BackgroundDespite extensive molecular epidemiological studies, the prevalence and characteristics of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) in Chinese women breast cancer are still unclear. Besides, the prevalence of MMTV-LV in women breast cancer tissue varies in different countries and its dependent factors remain inconclusive.MethodsIn the first part of the study, a case-control study was performed. 119 breast cancer samples (84 from Northern China and 35 from Southern China) and 50 breast fibroadenoma specimens were collected from Chinese women patients. MMTV-like env sequence and the homology to MMTV env gene were analysed by semi-nested polymerase chain reaction (PCR). We also explored the association of MMTV-LV prevalence with sample sources (Southern and Northern China) and patients’ clinicopathological characteristics. To investigate the dependent factors of the prevalence of MMTV-LV in breast cancer worldwide, a meta-analysis was conducted in the second part of the study.ResultsWe found that the prevalence of MMTV-LV was much higher in breast cancer tissues (17.65%) than that in breast fibroadenoma specimens (4.00%) (P < 0.05). MMTV-LV prevalence in Chinese women breast cancer tissues was significantly different between Southern China (5.71%) and Northern China (22.62%) (P < 0.05). The prevalence of MMTV-LV also associates significantly with expression of HER2, but shows no significant correlation with other parameters. In the meta-analysis, we found that MMTV-LV prevalence in breast cancer tissue was dependent on the distribution of M. domesticus mouse (M. d), M. musculus mouse (M.m) and M.castaneus mouse (M.c) worldwide (P < 0.05).ConclusionThe distribution of house mice may be a crucial environmental factor that explains the geographic differences in human breast cancer incidence. Our findings may provide a potential avenue of prevention, diagnosis and treatment for breast cancer.
Highlights
Breast carcinoma is a leading cause of cancer mortality in women worldwide
Sequence homology analysis of the polymerase chain reaction (PCR) products To analyse the homology of PCR products to mammary tumor virus (MMTV) env gene, twelve PCR products randomly chosen from different specimens were sequenced
Our finding suggests that the role of mammary tumor virus-like virus (MMTV-LV) in human breast cancer may be correlated to the HER2 oncogenic pathway, but it remains to be confirmed in further molecular mechanism research
Summary
Breast carcinoma is a leading cause of cancer mortality in women worldwide. Many risk factors have been identified in the development of this tumor, such as diet, obesity, nulliparity, hormones, increased life expectancy and family history [1,2,3,4,5,6]. In the recent several years, studies using PCR method with primers from selected regions of the MMTV env gene screened MMTV-like sequences in human milk [13] and breast cancer specimens [16,17,18,19,20,21,22,23]. Various investigators have postulated that mouse mammary tumor virus-like virus (MMTV-LV), a similar virus to MMTV, might be a cause for human breast cancer [24,25,26,27]. Despite extensive molecular epidemiological studies, the prevalence and characteristics of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) in Chinese women breast cancer are still unclear. The prevalence of MMTV-LV in women breast cancer tissue varies in different countries and its dependent factors remain inconclusive
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