Can we “catch” breast cancer?

Third of five student guest posts by Dana Lowry

In 1911, Peyton Rous first discovered viruses can cause cancer.  A chicken with a lump in her breast had been brought to Rous by a farmer.  Rous prepared an extract that eliminated bacteria and tumor cells and injected this extract into other chickens—tumors grew.  Rous suggested “a minute parasitic organism” was causing the tumor growth, which is now known to be a virus.  However, Rous’ discovery remained very controversial, and it wasn’t until 1966 that he was awarded a Nobel Prize for his discovery.  Since Rous’s discovery, researchers have found an estimated 15 percent of all cancers worldwide are associated with viruses.  Some common virus and cancer associations are: human papilloma virus (HPV) and cervical cancer, hepatitis B and liver cancer and human T lymphotropic virus type 1 (HTLV-1) and T-cell leukemia.

Epstein-Barr virus (EBV), a member of the herpesvirus family, is one of the most common viruses worldwide.  Among 35 to 40 year olds in the U.S., up to 95% have been infected with EBV.  Oftentimes, children infected with EBV have no clinical signs or symptoms; however, 30% to 50% of adolescents and young adults exposed to EBV for the first time will develop infectious mononucleosis, commonly known as mono.  In the U.S., individuals are usually exposed to EBV in adolescence or young adulthood compared to developing countries, where oftentimes individuals are exposed as infants or young children.  EBV usually remains dormant in the body throughout an individual’s lifetime, similar to the varicella-zoster virus, the virus responsible for the chicken pox.  EBV is known to play a role in Burkitt ’s lymphoma (cancer of the immune cells), nasopharyngeal cancer (cancer of the upper throat) and Hodgkin’s lymphoma (cancer of the lymphatic system), but can EBV also play a role in breast cancer?

In 2010, James Lawson and Benjamin Heng reviewed 27 papers concerning EBV and breast cancer associations. EBV infections are universal in high and low risk breast cancer groups, making it unlikely that EBV is the sole contributor to forms of breast cancer [1].  However, the age at which EBV is contracted seems to play a role in the risk of developing breast cancer. Women in Western countries are at higher risk of developing breast cancer and tend to be infected with EBV during adolescence or young adulthood, whereas women from non-Western countries have a lower risk for developing breast cancer and tend be infected during infancy or early childhood.  Hodgkin’s lymphoma shares a similar correlation with higher rates in Western countries [2].  Although there seems to be a relationship between age of EBV infections and risk of breast cancer, potential confounders need to be considered.  Women in developing countries tend to have more children, have children at a younger age and breastfeed their children for longer periods of time.  Breastfeeding, having more children and having children earlier in life all seem to be protective factors against breast cancer.

Beyond epidemiological evidence, lies biological evidence.  Twenty two of the studies Lawson and Heng reviewed were based on polymerase chain reaction (PCR) techniques. Issues have been found with standard PCR procedures, but it is becoming widely accepted that EBV can be identified in breast cancer tissue through specific PCR techniques [1].  EBV genes have been found in breast cancers through polymerase chain reaction (PCR) analyses.  EBV has not only been shown to shed in human breast milk [3], but it has also been shown to stimulate growth of human breast-milk cells [4]. The mechanism by which EBV actually causes cell alterations is not known, but it is thought to be different from the mechanisms used in lymphomas and nasopharyngeal cancer [1].

It is unlikely that we can actually “catch” breast cancer, as EBV doesn’t seem to be the sole cause of breast cancer.  EBV may contribute to breast cancer by altering genes in the breast cells which eventually leads the uncontrolled cell division, known as cancer.  More importantly, it seems the age an individual is infected with EBV may play an even bigger role in the outcome of disease.  An EBV vaccination is in the works that will hopefully prevent infectious mononucleosis and EBV-associated cancers.  However, the vaccination may not prevent the EBV infection itself; it is targeted towards the most abundant protein on the virus and on virus-infected cells.  If the vaccination proves to be successful, it will be interesting to see if a reduction in breast cancer rates will follow, along with the known cancers associated with EBV. Only time will tell.

 

References:

  1. Lawson, J. and Heng, B. (2010). Viruses and Breast Cancer. Cancers 2010, 2(2), 752-772; doi: 10.3390/cancers2020752.

 

  1. Yasui et al. (2001). Breast cancer risk and “delayed” primary Epstein-Barr virus infection. Cancer Epidemiology, Biomarkers & Prevention, 10:9-16. http://cebp.aacrjournals.org/content/ 10/1/9.long.

 

  1. Junker et al. Epstein-Barr virus shedding in breast milk. (1991). The American Journal of the Medical Sciences, 302: 220–223. http://www.ncbi.nlm.nih.gov/pubmed/1656752.

 

  1. Xue et al. (2003). Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?. British Journal of Cancer, 89:113–119. http://www.nature.com/bjc/journal/ v89/n1/full/6601027a.html

 

 

What might have caused my cousin’s nasopharyngeal carcinoma

Student guest post by Anh To.

When I found out my only non-smoking cousin had nasopharyngeal carcinoma (NPC), I was puzzled. With all the hype about cigarette smoking associated with various kinds of cancers in the media, I did not understand why none of my smoking cousins had NPC but the one who didn’t smoke did. At first, I thought it must be due to the second hand smoke. Now, I understand that the picture is very complex.

Before I go into what I have learned over the past several months, I need to make a disclaimer. I am not an expert in NPC. I am an average college student. This is what I have learned.

Back to my story, the first thing I did when I heard the news was to do a search on what NPC is and what are some of the current risk factors associated with it. According to the American Cancer Society (ACS), NPC arises from epithelial cells of the nasopharynx. There are three types of NPC, keratinizing squamous, non-keratinizing and undifferentiated. Keratinizing is more common in the US, whereas undifferentiated is more common in Asia (1). My cousin is in SE Asia, it made sense that he had undifferentiated carcinoma.

Unsurprisingly, I found that NPC has both genetic and environmental contributing factors. In genetic factors, there are strong associations with a family history of NPC and being male (1); there are also some associations with certain Human Leukocyte Antigen (HLA) types and/or the CYP2E1 gene (1, 2). HLA is the name for major histocompatibility complex (MHC) in humans. MHC is part of the immune system. Thus, certain HLA makes people vulnerable to all kind of diseases, including NPC. CYP2E1 is a member of the cytochrome P450 superfamily of enzymes which metabolizes many substances (6). Homozygous for certain allelic version of CYP2E1 was associated with NPC in a case-control study (2). It is proposed that CYP2E1 metabolizes nitrosamine, which is converted from nitrites and secondary amines from proteins, into a carcinogenic form inside the body (5). In environmental factors, the strongest associations are Epstein-Barr Virus (EBV) infection and consumption of “salted fish”, which was a common dish in Southern China, where one of the highest incidences of NPC occurred.

My cousin is a man, and we have a family history of NPC. Genetically, he was out of luck. However, I have many male cousins, but not all of them got NPC, therefore environment must have a big role in the causation. My other reason for learning more about environmental contributing factors was that I want to know what I can do to reduce my risks. I can’t change my genes, but I can modify my environment.

The two commonly accepted environmental contributions of NPC are EBV infection and consumption of “salted fish”. First, let’s focus on EBV. EBV is a member of the herpes family, which means it has a lysogencic (resting) and a lytic (active) phase. EBV infection prevalence is very high all over the world. As an infectious disease agent, it is associated with mononucleosis (kissing disease). As a chronic disease agent, EBV has been associated with nasopharyngeal carcinoma, Burkitt’s lymphoma and is being investigated for association with multiple sclerosis.

According to the CDC website, as many as 95% of adult American (between the ages of 35-40) has EBV, I’m not that old yet, but the chance that I already have or will have EBV infection is really high. Since I can’t do much to change my risk of exposure to EBV, let see if I can reduce my consumption of “salted fish”.

I didn’t know what this “salted fish” is and what makes it a contributing factor for NPC. The first evidence I found that links it to NPC was two papers written by Xi Zheng et al. The first indicated that EBV is the most important factor for NPC with “salted fish” in second place (3). The second suggested that there is interaction between EBV and something in “salted fish” that induced tumor growth since higher proliferation in non-tumorigenic human keratinocyte line in vitro (culture cells) was observed in cells infected with EBV that is incubated with “salted fish” extract than without(4).
Later study indicated that the something in “salted fish” was nitrosamine, a known carcinogen in many animal models (2). This is where second-hand cigarette’s smoking came into play. While I didn’t find any study that stated that cigarette smoking is a significant contribution to NPC, there is nitrosamine in cigarettes. I believe that my cousin’s NPC was partially caused by his being around my smoking cousins. Of course, I have no epidemiology evidence for it. I also realize that this is just a tiny part of the whole picture.

So far, I have learned that HLA, CYP2E1, EBV, and nitrosamine, are some of the contributing factors, I still don’t know the rest of the contributing factors or how they all interact with each other. However, now I know that while I can’t do much about HLA, CYP2E1, or EBV, I can certainly reduce my exposure to nitrosamine through checking labels and selecting food with low nitrosamine as well as avoiding cigarette smoke.
As for my cousin, he finished his chemo and radiation therapy. His cancer is in remission. However, I don’t know if or when it will come back.

References

1. Detailed Guide: Nasopharyngeal Cancer. American Cancer Society. Accessed on 2/16/2010 Link

2. Ward, Mary and et al. Dietary Exposure to Nitrite and Nitrosamines and risk of Nasopharyngeal Carcinoma in Taiwan. Int. J. Cancer: 86, 603-609 (2000).

3. Zheng, Xi, Luo Yan, Bo Nilsson, Gunnar Eklund and Borje Drettner. Epstein-Barr Virus Infection, Salted Fish and Nasopharyngeal Carcinoma. Acta Oncologica Vol. 33, No. 8, 867-872 (1994).

4. Zheng, Xi and et al. Studies on Etiological Factors of Nasopharyngeal Carcinoma. Acta Otolaryngol (Stockh) 113, 455-457 (1993).

5. Hildesheim, A. et al. CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan. J. Natl Cancer Inst 89, 1207-1212 (1997)

6. Cytochrome P450, family 2, subfamily E, polypeptide 1. Accessed on 2/16/2010 Link