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.


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


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"salted fish" probably refers to fish preserved by salting, as in pickled herring or salt cod.

Cod, being a very low-fat fish, was commonly preserved by salting and drying. This produced a very durable product that would keep for long periods of time at room temperature and could be reconstituted simply by soaking in water to desalinate it- perfect for shipboard use and also for feeding an army in the days before canning and mechanical refrigeration.

Salt cod also became a staple food in the Caribbean and in Europe (the French, Spanish and Portugese words for "cod" have the specific meaning of "salt cod"). As a durable, inexpensive high-protein food it might also have become popular in Asia.

Check out Mark Kurlansky's book "Cod: A Biography of the Fish that Changed the World". It's very informative and it has recipes.

By Ktesibios (not verified) on 23 Feb 2010 #permalink

My boyfriend just passed away at the age of 19 because of NPC. His family still doesn't know where he got it. He doesn't smoke or around smokers. He doesnt even have family history of NPC. Its still a mystery to us. He was perfectly fine last year in april. Before april though he was having alot of neck pain.

HPV is gaining as a suspect in many NPC cases, too

Epstein Barr is also causal in a number of lymphoma's (subtypes of both Hodgkin's and Non-Hodgkin's). This virus gave me mixed cellularity Hodgkin's lymphoma.

Epstein Barr hides in the body and reactivates once in a while. In my case the reactivation was always associated with winter and spring and latency with summer. I raised my vitamin d levels and the cycle stopped (these episodes occurred before and after my treatment for Hodgkin's and each time left me with hard lumpy lymph nodes). The lumps probably contain latent Epstein Barr infected B cells surrounded by other immune cells. Once these lumps turned in to a lymphoma. A number of years later I saw an article showing that vitamin d formed an important part of the innate immune system and it is probably helping hold the virus in its latent state.

I would recommend anyone who has had trouble with Epstein Barr to get their vitamin d levels checked and raised to at least 50ng/mL. Farmers/beach guards often have levels of 100ng/mL so it is fairly normal. In most people it seems to take about 5,000IU of d3 a day to maintain these levels. It is worth a try.

average college student - that u are not.
do not hide ur light.
please do not play candyflossgames with false statements. it's for small kidz.

By jon edvard killi (not verified) on 01 Apr 2010 #permalink

Very good article. I too have had NPC - I do smoke and do drink like a fish - but .... I really do not think that caused it, but OK, it didn't help. y problem is the after effects - I am 2 years clear, but still going through hell - anyone else ?