Is breast cancer in Barbados infectious?

The concept that a virus is involved in the genesis and development of breast cancer has been proposed and held in scientific discussions for many years. In fact Dr. Bittner in 1936 was the first to described the causative agent of breast cancer in mice, the mouse mammary tumour virus (MMTV).

Many studies in the 1970s and 1980s have proven the presence of MMTV-like sequences in breast cancer samples but the notable absence from normal breast tissues. Serological studies proved that antibodies raised against this virus could be found in breast cancer patients. Furthermore viral particles with characteristics of a retrovirus were observed in samples of breast milk (60%) from breast cancer patients.

However the possibility of a virus causing breast cancer has not been without challenges and scientific opposition. There were a number of studies failing to find the viral sequences in breast cancer samples which have been reported. One study presented data which showed that the human genome contains retroviral sequences that are 50% homologous to MMTV. Another study found MMTV like virus in a pool of 300 normal breast milk samples.

The possibility of DNA contamination from rodents namely mice was advanced as the reason for positive detection of these sequences and absences in other studies. The variation in detection could very well be due to variation due to geographical location.

Questions remain on the origin of MMTV sequences detected in human breast cancer. It has been suggested that these sequences represent a human form of MMTV, others have suggested that these sequences are not, in fact, a separate virus, but rather MMTV acting as a zoonotic virus.

Breast Cancer Virus - Human Mammary Tumour Virus

A number of studies have been conducted on the possible role of an infectious agent in the causation of breast cancer. These studies have suggested the possible role of a virus related to a rodent borne mouse mammary tumour virus (MMTV; http://en.wikipedia.org/wiki/Mouse_mammary_tumor_virus) in association with human breast cancer tumours. The investigators identified a "..complete proviral sequence that was greater than 95% homologous to MMTV was sequenced out of human breast cancer tissue including a correct integration into the human genome." It was thence named Human Mammary Tumor Virus (HMTV). HMTV is a retrovirus (HIV is also a retrovirus) that inserts itself into human DNA and causes expression of a number of proteins that can alter hormonal levels and lead to subsequent tumour development.

HMTV may also be linked with other human diseases including leukemia since human breast cancer has been correlated with leukemia and HTMV's viral sequence has been found in this form of cancer.

Few if any studies have been conducted in rodents and the incidence of MMTV in localised mice populations. A number of other factors have been linked to increased risks of developing breast cancer including use of birth control pills, diet, lack of exercise, obesity, age at time of child birth, environmental exposure to carcinogens etc. Is there a mode of transmission from mice to humans where tumours are associated with HMTV? Only sound scientific evidence would be able to substantiate this.

To establish such evidence investigations of mice reservoir should be conducted to determine MMTV incidence within a localized region and or country. The samples obtained should yield good genomic data that could be used at a later date for comparison with viral DNA from human breast cancer tumours to determine the degree of viral strain relatedness.

Human studies using breast cancer tissues and normal tissues should be conducted to determine the incidence in humans both in the affected population and normal healthy population.

HMTV viral data should be compared with those already deposited in GenBank to assess relatedness with HMTV strains found in other parts of the world. Mice have a wide global geographical distribution yet there appears to be higher breast cancer incidence in populations of African descent than in Native American, Asian or Caucausian populations. The role of BRCA genes has partially explained this disparity but it remains to be seen if HMTV inserted into DNA of affected individuals is responsible for the switching on and off critical molecular pathways that alter hormonal levels in the body promoting tumour development.

It would be advantageous if such research is lent the necessary support that would allow a clearer perspective on this disease that affects millions worldwide.

XMRV - A New Prostate cancer virus?

In 2006 some US researchers (see http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0020025) have unearthed evidence of a possible viral link to prostate cancer, yes prostate cancer! For years the primary belief that prostate cancer was exclusively caused by a number of factors including genetic, dietic and environmental has seemingly been dealt a strong blow. The aetiological (causative) complexity of cancer in its many forms suggest multifactorial causes however most of the scientific community has been slow and reluctant to accept microbial or infectious causes for cancers. The recent work involving HPV, the virus causing cervical cancer, has seemingly softened this stance. Nonetheless the caution exhibited is necessary since sound science is always founded on strict and unwaivering proof that is both reproducible and logical.

This leads to the most recent candidate for an infectious agent of prostate cancer, XMRV. The authors presented the first documented evidence of XMRV, a xenotrophic retrovirus in subset of human prostatic samples. Furthermore they proved that the virus XMRV was capable of replicating in human cells and this replication is regulated by interferon (IFN) and its downstream effector gene RNase L. The role of RNase L a gene coding for a unique ribonuclease that is essential in the production of interferon and XMRV was later investigated by this group of scientists.
This investigation showed a difference in the variation of this gene and the incidence of XMRV infection, where homozygous (QQ) recessive forms of the gene had higher incidence (40%) of infection than heterozygous (RQ) or homozygous dominant (RR) forms (1.5%) of the gene.

Notwithstanding some skepticism and reservation for full acceptance of this virus as a cause of prostate cancer still exists. Studies from researchers in Germany have failed to reproduce the levels of incidence of XMRV infection in prostate samples or even establish the presence of XMRV in German patients. From previous studies the genetic make-up (Rnase L gene) of the cohort appears to influence XMRV incidence. Another group of US researchers did find XMRV infection in prostate cancer patients albeit at a lower incidence than that originally found (40% vs 6%). They found "...XMRV infection to be independent of a common polymorphism in the RNASEL gene, unlike results previously reported"." In addition they found that the association was greater with higher grade tumours. (http://www.pnas.org/content/106/38/16351.abstract)


There are a number of questions which remain unanswered. These include how does a man become infected with XMRV? What is the reservoir or source of this virus? How can a man protect himself from becoming infected? What is the mode of transmission (sexual, respiratory, blood borne etc)? Future studies involving patients in different geographic areas to investigate the prevalence of XMRV not only in prostate cancer patients but also in healthy individuals both male and female and possible animal reservoirs could offer more insight into the mode of transmission.

This possible candidate for prostate cancer underscores the dynamic nature of the knowledge of the interaction between man and viruses in the environment.