Letters to the Editor
To the Editor:
I am writing to you because I am interested in the work published in a recent article in your journal (Deligdisch L, Marin T, Lee AT, et al. Human Mammary Tumor Virus [HMTV] in Endometrial Carcinoma. Int J Gynecol Cancer. 2013. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/23873177).
I am a viral epidemiologist and also quite familiar with epidemiological investigations of cancer and illnesses related to “environmental” factors such as smoking, drinking, exposure to UV from sun, or living in proximity to industrial pollution. I primarily work on the epidemiology of HIV-1 and hepatitis C virus, but my experience with those viruses and a few others has made me acutely aware of how we can trace the spread of viruses and the spread of illnesses caused by those viruses even when the virus is only loosely linked to a disease, or there is a large temporal lag between infection and disease.
I also have studied many cases of polymerase chain reaction contamination and false results. Most of the cases I have followed are HIV-1, but I am also well aware of the XMRV story and many other human cancer virus (“rumor virus” not tumor virus1,2) stories. I am quite dismayed that the public opinion and politics seem to be more influential than science in influencing how research into these viruses is or is not done. The story of XMRV as a cause of prostate cancer was not fully investigated until it was also implicated in, for example, chronic fatigue syndrome.3–5 The story of Human Mammary Tumor Virus is essentially identical to the story of XMRV except that it has not yet been implicated in diseases other than cancers.
Retroviruses usually do not jump from one host species to another. If many humans have become infected with any mouse retrovirus, then the epidemiology needs to be investigated. Linking a virus to a disease is also not completely simple in many cases. For example, although it is abundantly clear that hepatitis C virus causes liver cancer, not all strains are equally carcinogenic, and not all people infected with even the most carcinogenic strains develop liver cancer.
With the alleged human mammary tumor virus, it is not enough to publish dozens of articles showing that laboratories can create polymerase chain reaction products from tumors but not normal cells. One simple requirement should be a panel of double-blinded samples and controls tested by at least 2 laboratories. The results of one such study, for example,6 proved that the laboratory preparing the samples contaminated some of the negative controls.
If murine viruses are involved in even 1% of human mammary cancer or 1% of human uterine cancer cases, then it likely represents millions of humans infected with a murine retrovirus. Determining how humans came to be infected would then be of critical importance. Is handling dead mice from mousetraps risky? Are laboratory workers who work with MMTV at high risk of cancer? Could MMTV be spread in food when mice come in contact with grains in warehouses? Are some of our vaccines contaminated by cell cultures infected with MMTV? Can MMTV truly become human mammary tumor virus and spread from human to human (eg, mother to infant)? Or is it always directly from mouse to human and never further human-to-human spread? These are all questions that urgently need to be investigated if a set of double-blinded samples and controls indicates that the virus is actually present in any human cancers.
Brian T. Foley, PhD
Los Alamos National Laboratory
Los Alamos, NM
1. Voisset C, Weiss RA, Griffiths DJ. Human RNA “rumor” viruses: the search for novel human retroviruses in chronic disease. Microbiol Mol Biol Rev
. 2008; 72: 157–196.
2. Tuke PW, Tettmar KI, Tamuri A, et al. PCR master mixes harbour murine DNA sequences. Caveat emptor! PLoS One
. 2011; 6. Epub 2011 May 25.
3. Hué S, Gray ER, Gall A, et al. Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology
. 2010; 7: 111.
4. Zheng H, Jia H, Shankar A, et al. Detection of murine leukemia virus or mouse DNA in commercial RT-PCR reagents and human DNAs. PLoS One
. 2011; 6. Epub 2011 Dec 20.
5. Erlwein O, Robinson MJ, Dustan S, et al. DNA extraction columns contaminated with murine sequences. PLoS One
. 2011; 6. Epub 2011 Aug 18.
6. Strickler HD; International SV40 Working Group. A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens. Cancer Epidemiol Biomarkers Prev
. 2001; 10: 523–532.