Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, District Wardha, Maharashtra, India.
Breast Cancer Res Treat. 2012 Aug;135(1):1-15. doi: 10.1007/s10549-011-1921-4. Epub 2012 Jan 25.
The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.
三种最有可能导致人类乳腺癌的病毒是鼠乳腺肿瘤病毒样序列（MMTV-LS）、爱泼斯坦-巴尔病毒（EBV）和致癌（高危型）人乳头瘤病毒（HPV）。要满足推断癌症是由病毒引起的传统标准，第一步是在受影响的组织中证明病毒的存在。与宿主抗体评估和免疫组织化学相比，分子技术在确定病毒存在方面最为明确。对 85 项原始分子研究调查结果进行了评估，以检测三种病毒中的一种或多种病毒，结果差异极大，没有达成共识。我们评估了这些研究的方法学：分子检测的类型、DNA/RNA 质量控制、阳性和阴性检测对照、固定类型、基因组靶标、防止和检测分子污染的方法、处理标本的病理学、样本量以及针对目标病毒基因组区域的标本阳性比例。只有 7 项研究令人信服地证明了致癌病毒生物标志物的存在（EBV：30 项研究中的 4 项（13%）；HPV：29 项研究中的 3 项（10%），而 25 项研究令人信服地证明了所研究的病毒不存在（MMTV-LS：25 项研究中的 4 项（16%）；EBV：30 项研究中的 15 项（50%）；29 项研究中的 6 项（21%））。其余研究存在缺陷，在我们看来，这些缺陷阻止了明确的结论。只有一项研究将病毒在乳腺癌患者和无乳腺癌病史的适当正常对照乳房组织中的频率进行了比较。没有一项研究是作为流行病学研究设计的，以确定病毒的存在是否与乳腺癌显著相关。基于我们的评估，这里综述的出版物中的数据仍然是初步的，不能得出 MMTV-LS、HPV 或 EBV 与乳腺癌有因果关系的结论。然而，它们为指导未来的研究提供了有价值的基础。
