Student guest post: Cancer isn’t contagious…or is it??

Student guest post by McKenzie Steger

Off the southeastern coast of Australia lies a small island that in the 1700 and 1800’s was inhabited by the very worst of Europe’s criminals and is now the only natural home in the world to a species named after the devil himself. Decades later beginning in 1996 Tasmanian devils were going about their nocturnal lifestyle in normal devilish fashion feasting on small mammals and birds, finding mates and reproducing, occasionally fighting with one another and so on. (1) Just as criminals divvied up their booty hundreds of years before, the devils were sharing something of their own—only something of much less value. It turns out they were transmitting to one another a rare and contagious form of cancer known as Devil Facial Tumor Disease or DFTD. Once infected, facial tumors developed and the devil faced 100% mortality most often due to inability to eat or airway obstruction. Over the last 17 years the result of this highly contagious and fatal cancer has been the elimination of over half of the devil population throughout Tasmania. (2)

mckenzie picture


DFTD is not alone when it comes to transmissible forms of cancer. For over six thousand years dogs, jackals, wolves, and coyotes across the globe have experienced their own “contagious” cancer in the form of canine transmissible venereal tumor—C TVT and also called Sticker’s sarcoma. (2) CTVT is generally considered the first known cell line to be malignant having been described in the mid 1800’s. These unique growths like DFTD can spread from one individual to the next, but in the case of CTVT this most commonly occurs during coitus, licking, and biting infected areas. CTVT lesions usually establish in the genitals or in close proximity as a result. CTVT is unique in that only an estimated 7% of cases metastasize unlike in DFTD cases where 65% of them result in metastasis. CTVT rarely results in severe clinical illness but instead nearly always regresses on its own. (3)

So what is it that makes DFTD and CTVT so “contagious”? Essentially it boils down to host immunity. In the case of DFTD, devils pass on tumor cells when they are in close physical contact with others during mating or fighting. The Tasmanian devil population simply lacks the genetic diversity to be able to immunologically recognize and ward off the tumor and thus, these highly virulent and metastatic cells set up camp in the new host tissue and invade in no time. Interestingly, studies have shown that the DFTD cells are unique, containing only 13 pairs of chromosomes instead of 14 like most cells. Technology has also shown the very same cell line that began the DFTD devastation—thought to be of Schwann cell origin—is the very same one being transmitted throughout devil populations today. (2)

In contrast, CTVT, a histiocytic tumor (4), affects mammals rather than marsupials which have much greater diversity within the population and a more advanced capability to detect foreign and potentially invasive cells. This is due to the MHC-1 molecules or multiple histocompatibility complexes that help the body’s immune system to recognize foreign substances. CTVT is so effective in transmission because it down regulates these MHC-1 molecules effectively “hiding” the invasive cells from the body’s immune system. At some point however, this mechanism is overcome and the CTVT is recognized and killed by the body in animals that are immunologically sound. (2)

What about transmissible cancer in humans? The good news is that no comparable strain of such a killer contagious cancer has been recognized in humans compared to what devils in the “land down under” are experiencing. The bad news is that there are technically forms of cancer affecting man that result from contagious agents. Estimations attribute 15% of tumors world-wide to contagious pathogens including mainly viruses but also bacteria and parasites as well. Most documentation of cancer transmission cases in humans are reported in individual case reports, however, highlighting the rarity and unlikelihood of this occurrence. (2) Nonetheless, it still occurs. Hepatitis B and C viruses, herpes viruses, human immunodeficiency virus (HIV), and papilloma viruses are just a few examples of viruses that can develop into cancer in patients or predispose them to tumor formation. Bacterial etiologies include members of the Chlamydia, Helicobacter, Borellia, and Campylobacter families. There are also a few select parasites classified as Group I and Group II carcinogens including members of the Schistosoma, Opisthorchis, and Clonorchis families. So really, “contagious cancer” in humans is due to contagious or infectious etiologies and not necessarily direct contact transmission. Although there are documented and potential exceptions including cancer spread through tissue grafts, organ transplants, papillomavirus transmission during sexual intercourse and other isolated events. (1)

At the end of the day, the presence, history, transmission, and pathogenesis of transmissible cancers in Tasmanian devils, dogs, and the few cases documented in humans provides insight regarding the immune mechanisms that do and those that do not allow cancer to develop. The key difference here is mammals verses marsupials and the reality that mammals have a more advanced immune system allowing them to better overcome cancer and other foreign invasions. A better understanding of both CTVT and DFTD has and will likely continue to allow researchers better insight into mechanisms of immune system invasion of various types of cancer. (1)



(2)   Welsh JS. Contagious Cancer. Oncologist. 2011 January; 16(1): 1–4. Published online 2011 January 6.

(3)   Belov K. Contagious cancer: Lessons from the devil and the dog. BioEssays: Volume 34 (4), pages 285–292, April 2012.



Student guest post: Cholesterol, a bacterium, and gallbladder cancer

It’s time for this year’s second installment of student guest posts for my class on infectious causes of chronic disease. Fourth one this round is by Kristen Coleman. 

If you are anything like me, you have been told countless reasons over the years why we must watch what we eat, keep our cholesterol intake down, and try to work out. It shouldn’t really come as a surprise then that I, since I am a public health student after all, aim to convince you of yet another reason why a healthy diet and exercise are valuable. What is this huge reason to avoid Big Macs and think about taking the stairs instead of the elevator you ask? Well, it may help you to prevent gall bladder cancer, is all.

All of this begins with gallstone formation. Gallstones are hard deposits, usually of cholesterol, that become lodged in your gallbladder over time. Your gallbladder is an organ that helps to aid in digestion through the storage and release of bile which helps to break down fats in your small intestine. The gallbladder is located on the right side of the body attached to the liver. The process of gallstone formation is called cholelithiasis. In this process, cholesterol, which is not very soluble, becomes clustered together in droplets in the bile called micelles. This cholesterol droplet then hardens into the crystals that make up a gallstone. Obesity causes bile to transit the gallbladder less rapidly and increased cholesterol in the diet means there is more cholesterol available to form stones. It does not require and active imagination then, to understand how obesity and high cholesterol intake contribute to stone formation, but how does this all tie into cancer you ask?

It all comes down to infection with a bacterium known as Salmonella typhi. Yes, this is the same bacterium that causes Typhoid fever and was the malady that afflicted the famous Typhoid Mary. While many people may become infected with S. typhi over the course of their lives, those individuals with gallstones are 6-15 times more likely to become carriers of S. typhi in the gallbladder. This is important because those people with a chronic infection of S. typhi have been shown to have 3-200 times higher risk of developing gallbladder cancer then non-carriers. Furthermore, chronic carriers have a 1-6% lifetime risk of developing gallbladder cancer. In fact, gallbladder cancer is so linked to S. typhi infection that gallbladder removal, called cholecystectomy, is recommended for those people with gallstone disease who live in high risk areas. Where is a high risk area? Most developing countries of the world are high risk areas for S. typhi, especially countries in Asia, Africa, and Latin America. This means that travelers from the USA and other developed countries to these regions are at risk for developing the infection. However, even at home in the USA, low risk doesn’t mean no risk, and we should be vigilant against emergence of this bacterium.  

In conclusion for all my gallbladder-containing friends out there (I make this distinction because I, myself, am no longer at risk for gallbladder cancer since I had mine removed in 2006 after a bout with gallstone disease) stay aware of your cholesterol levels and pay attention to making sure you have a healthy diet because, like every health care professional will tell you, it might just save your life….perhaps in a way you don’t expect!


  1. University of Maryland Medical Center. Gallstones and gallbladder disease. Online
  2. Ferreccio, Catterina. Salmonella typhi and Gallbladder Cancer.

Center for Disease Control online source.

Student Guest Post: Arsenic, Benzene, and Now Clostridium? Smokers are Inhaling More Than Just Chemicals in Their Cigarettes

It’s time for this year’s second installment of student guest posts for my class on infectious causes of chronic disease. Second one this round is by Jonathan Yuska. 

If you happen to be one of the 46 million individuals who have not been swayed to quit smoking by the countless anti-cigarette ads in print and on television, here is one more piece of evidence that may have you second thinking that next puff. On top of the more than 3,000 chemicals and heavy metals already identified in ordinary cigarettes1, upwards of a million microorganisms per cigarette have also been found to live and thrive in virtually all cigarettes in the United States2. Microbes such as Bacillus (which is linked to the notorious anthrax disease), Clostridium, and Pseudomonas—to name a few—likely contaminate the tobacco leaves early at the farm level and are able to flourish during curing and manufacturing to be viable in the cigarette at the time of the consumer’s use. While some of the bacteria are capable of causing no more than a stomachache, others (and their respective endotoxins) have been linked to pneumonia and chronic lung inflammation—a widely recognized risk factor for cancer1,2. While cigarette smoking is a well-established cause of cancer in and of itself, the role microorganisms have in the toxicity of cigarette smoke should not go underplayed. With increasing evidence supporting the vast illness causing biodiversity found in cigarettes, hopefully more individuals will be aware of the dangerous contaminants they are welcoming into their bodies and call for greater sanitary measures to be taken to potentially create a less harmful cigarette product.

Approximately 23 different species of bacteria have been found in cigarette tobacco, many of which have been linked to serious illness in humans. For example, Pseudomonas aeruginosawhich is the leading cause of nosocomial pneumonia and often found in soil or sand—was found to be present in nearly all cigarettes tested in a study that looked at the presence of cigarette bacteria in the most commonly smoked brands, like Marlboro2. Another study interested in understanding the cause of severe lung inflammation in United States troops during Operation Iraqi Freedom found eight different species of Bacillus (five of which were never seen before) contaminating the soldier’s cigarettes3. Regardless of the actual bacteria within the cigarettes, the endotoxins derived from the bacteria that remain well after the bacteria have died have been shown to be a powerful inducer of lung inflammation (chronic inflammation is recognized as a powerful risk factor for cancer). It is theorized that the bacteria and their respective endotoxins may have an additive or multiplicative effect with tobacco smoke’s natural ability to cause pulmonary inflammation, though the amount of the effect that can be attributed is still up to debate2.

Research has shown that more than 90 percent of cigarettes are contaminated with some form of bacteria, and these bacteria are believed to originate early in the cigarette manufacturing process1. Similar to other crop cultivation, tobacco is grown in large fields where animal manure is used to provide the nutrients needed for a hearty crop. Some of the bacteria from the manure are believed to adhere to the tobacco leaves during the plant’s development. Curing the tobacco, which is essential in the cigarette manufacturing process to develop an ignitable, flavorful product, further facilitates bacterial growth because it is often done in moist, warm conditions3. Unlike other agriculture crops grown for consumption, tobacco has no regulations associated with its sanitation, and as a result, tobacco products can contain soil residues and insecticides in addition to a vast array of deleterious bacteria. Efforts to sanitize tobacco through an antimicrobial wash have been proven to be effective in reducing contaminants; however, since so little mainstream attention has been given to microbes in cigarettes, no sanitation process is currently being used by the cigarette industry2.

Misperceptions about how much risk the bacteria pose to the smoker is one reason so little attention has been given to microbes in cigarettes.  Some critics believe that bacteria in cigarettes pose no harm because the cigarette flakes are prevented from entering the lungs because of the built-in filter within the cigarette. Some further argue that the viable bacteria found in the tobacco are destroyed or heavily reduced in number by the heat of the cigarette. Though, the validity of these observations are derailed by the fact in the process of transportation, or even minor jostling, tobacco flakes are often seen lying freely on the mouth end of the filter. Thus, loose tobacco on filters could transfer bacteria to the mouths and lungs of smokers before the cigarette is even lit. Additionally, some extremely fine tobacco microparticulates are able to pass through the cigarette filters currently being used and can be inhaled deep into the lungs to cause inflammation2,5. The harsh, high temperature conditions of cigarette smoking also does little in eliminating the bacteria that are able to produce robust heat resistant endospores such as the bacterial species Bacillus and Clostridium1. It is clear that more attention should be given to dismiss the misperceptions of bacterial risk associated with cigarettes so that effective sanitary regulations can be applied to tobacco similar to other widely consumed foodstuffs.

If the more than 3,000 chemicals and heavy metals that have been identified in ordinary cigarettes have not influenced you to quit smoking, hopefully the realization that one cigarette can contain roughly 1,000,000 microorganisms will have you second thinking the habit the next time you light up. Microorganisms that have been linked to serious illness in humans like pneumonia and chronic inflammation are thought to contaminate tobacco leaves early in the manufacturing process, and these organisms thrive and multiply to be viable bacteria in the consumer cigarette. While cigarettes themselves are recognized as a serious cause of ill health, the role microorganisms have in their toxicity should not be underplayed. With a better understanding of the vast bacterial biodiversity within cigarettes, sanitary regulations that eliminate bacterial contamination should be mandated to potentially make a less harmful tobacco product. Though until then, people should recognize the dangerous bacterial contaminants they are welcoming into their bodies every time they light up.


1.   Sapkota, Amy R., Sibel Berger, and Timothy M. Vogel. “Human Pathogens

Abundant in the Bacterial Metagenome of Cigarettes.” National Center for Biotechnology Information. 22 Oct. 2009. U.S. National Library of Medicine. 13 Apr. 2013 <>.

2.  Pauly, J. L., J. D. Waight, and G. M. Paszkiewicz. “Tobacco flakes on cigarette filters

grow bacteria: A potential health risk to the smoker?” Tobacco Control. 18 Oct. 2007. 13 Apr. 2013 <>.

3. Rooney, Alejandro P., James L. Swezey, Donald T. Wicklow, and Matthew J. McAtee.

“Bacterial Species Diversity in Cigarettes Linked to an Investigation of Severe Pneumonitis in U.S. Military Personnel Deployed in Operation Iraqi Freedom.” Current Microbiology 51 (2005): 46-52.

4. “How to Grow Tobacco.” How To Grow Stuff. 23 Nov. 2007. 13 Apr. 2013


5. Pauly, John L., and Geraldine Paszkiewicz. “Cigarette Smoke, Bacteria, Mold,

Microbial Toxins, and Chronic Lung Inflammation.” National Center for Biotechnology Information. 09 July 2011. U.S. National Library of Medicine. 13 Apr. 2013 <>.



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.



  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. 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.


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



Does bestiality increase your risk of penile cancer?

Aah, the things one learns when awake at 3AM on a Saturday night. Via a few different Tweeps, I ran across this article from Men’s Health magazine, titled “Urgent Warning: Sex with Animals Causes Cancer.”

I probably should have just stopped there.

But no, I read the magazine article, which states:

Brazilian researchers polled nearly 500 men from a dozen cities, and found that–we’re not joking around here–roughly 35 percent of the men had “made it” with an animal. That’s a problem, because screwing a horse, donkey, pig, or any other animal was found to up your likelihood of developing cancers of the penis by 42 percent.

Of course, this meant that now, I had to go dig up the actual journal manuscript. Though nothing is cited by Men’s Health, a quick PubMed search using the terms “sex with animals” and “Brazil” turned up Sex with Animals (SWA): Behavioral Characteristics and Possible Association with Penile Cancer. A Multicenter Study, published last month in The Journal of Sexual Medicine.

Though the MH write-up makes the research sound ridiculous, it’s not a bad paper overall. Starting out with the observation that penile cancer is common in impoverished regions in the world but relatively rare in developed areas, the authors wanted to examine one possible difference in this urban/rural divide: bestiality. So they enrolled 492 individuals who had spent their childhood in rural areas: 118 cases who had penile cancers and 374 controls who were seen at the same clinics for other issues, including check-ups and “cancer prevention” (though it’s not really defined what’s included in that catch-all). All participants were asked a variety of questions about their sexual history, including sex with animals and humans (frequency, number of partners, the usual drill), circumcision status, as well as other factors that might influence cancer outcomes, such as smoking status and history of sexually transmitted diseases and other health conditions.

The authors did find in the univariate analysis (basically, looking at one factor at a time) that there were several statistically significant differences between the cancer group and the control group. These included smoking, a history of sex with prostitutes, the presence of penile premalignant lesions (not surprising) and phimosis (NSFW), a condition where “the foreskin cannot be fully retracted over the glans penis.” As the title suggests, they also found that having sex with animals was significantly higher in the case than the control group (44.0 vs 31.6 percent, p<.008). When they combined risk factors into their multivariate analysis, a few factors still remained in the model. Phimosis was the big one, with an odds ratio of 10.41; SWA was down the list at 2.07 (95% CI: 1.21-3.52, p=0.007). Penile premalignant lesions and smoking also remained, with odds ratios in the middle of the other two. Finally, just because I know many of you out there are curious, they also break down those who have SWA by types of animals they, um, frequent:

The animal types most often cited were mares (N = 80), followed by donkeys (N = 73), mules (N = 57), goats (N = 54), chickens (N = 27), calves (N = 18), cows (N = 13), dogs (N = 10), sheep (N = 10), pigs (N = 6), and other species (N = 3).

Yes, chickens for 27 of them. I don’t even want to know, but I’m sure if I did, I could find out somewhere on the Internets. Please, don’t educate me on that one. They also note that almost a third of the men reported “SWA with a group of men.” I’m leaving that one alone as well (especially as that one wasn’t any different between cases and controls, so it didn’t seem to be an important variable for penile cancer development).

So how do they explain these findings? Their discussion is a bit odd, in my opinion, and narrows in on the SWA finding to the exclusion of their other significant risk factors. Of course, coming from my background, my first thought regarding SWA and cancer jumps to infectious agents. They acknowledge in the introduction that the human papillomavirus (HPV) is associated with about half of penile cancers. Other species of animals can also be infected with papillomaviruses, such as the rabbit of jackalope mythology. A previous study identified five potentially novel papillomaviruses in Australia, just by doing skin swabbing. As such, it’s certainly safe to say that we know very little about the diversity of these viruses that exist in other animal species, much less their cancer-causing potential. It would be fascinating to look at tumor samples from the men in this group who were known to have sex with animals, and see if any novel viruses (papillomas or otherwise) could be identified.

However, they don’t limit their suggestion to only zoonotic infections. That’s when it gets a bit weird to me, as they say things like:

Speculation exists regarding cancer status as an infectious disease in humans [24,25], as studies have suggested that tumor cells can be transmitted from one mammal host to another within the same species [26,27]. PC is frequent in equines [28], but transmission of malignancies between animals and humans has not been reported.Virology does not consider possible viral movement from animals to humans except in cases of zoonosis, such as rabies or pandemic forms of bird or swine flu. However, the hypothesis that the HIV epidemic resulted from simian-human virus transmission has not been fully explored.

Um, huh? First, the citation they use for the HIV claim is from 1999–indeed, at that point there was still a lot that was unknown about cross-species HIV transmission, but that was 12 years ago! The field has moved on since then. I’m baffled as to what they mean by their first sentence–as far as I know, “Virology” doesn’t consider anything–“Virologists” do, and why would this not be a zoonosis? Though I think direct transmission of cancer cells (like in the case of the Tasmanian devil transmissible cancer) would be unlikely, transmission of microbes which could lead to cancer development is certainly plausible and well within the realm of virology/bacteriology/etc. In my opinion, it’s infinitely more likely than the idea they also suggest of more directly carcinogenic animal secretions.

There were also a number of limitations in the paper. Though they grouped frequency of sex with prostitutes into a “more/less than ten times” dichotomous variable, I don’t see any similar “dose” analysis for the frequency of SWA in their models, even though they did ask the men about this. They make one statement that “long-term SWA (>3 years) was reported by 64% of the PC patients and 46.6% of the controls (P = 0.044).” This difference was statistically significant at the usual cutoff (p< .05), but it doesn't appear that they studied this further--why not? If you have a typical dose-response relationship (the more times the men had sex with animals, the more likely they were to develop cancer in the future), that would strengthen their case for a connection between the two. They also didn't ask about sexual orientation or the nature of the self-reported past STDs. Are any of these participants HIV positive, for example? Anyway, with these limitations in mind, it does appear that Men's Health got it mostly right: don't have sex with animals if you value your penis. But it's unfortunate that they just go for the sensationalism and ignore the more important variables from a public health standpoint, like "don't smoke" and "if you have abnormal penile conditions, you may want to get those checked out, k?" References

Zequi SD, Guimarães GC, da Fonseca FP, Ferreira U, de Matheus WE, Reis LO, Aita GA, Glina S, Fanni VS, Perez MD, Guidoni LR, Ortiz V, Nogueira L, de Almeida Rocha LC, Cuck G, da Costa WH, Moniz RR, Dantas Jr JH, Soares FA, & Lopes A (2011). Sex with Animals (SWA): Behavioral Characteristics and Possible Association with Penile Cancer. A Multicenter Study. The journal of sexual medicine PMID: 22023719

Antonsson and McMillan, 2006. Papillomavirus in healthy skin of Australian animals.

Potential for common bacteria to cause colorectal cancer

Student guest post by Desiré Christensen

Colorectal cancer (aka colon cancer) includes cancers of the colon, rectum, and appendix. Colorectal cancer is more common in developed countries (e.g. United States and Japan) compared to developing countries in Africa and Asia. Each year in the United States, there are around 150,000 cases of colorectal cancer diagnosed and about 50,000 people die from this cancer. Risk factors for colorectal cancer include lifestyle factors (e.g. habitual alcohol use; high-fat, low-fiber diet; obesity; sedentary lifestyle; smoking), family history of intestinal polyps or colorectal cancer, and medical conditions (e.g. diabetes, familial polyposis syndromes, hereditary non-polyposis colon cancer syndrome, inflammatory bowel disease, intestinal polyps). [1]

Lifestyle factors are considered important risk factors for colorectal cancer, and they are modifiable unlike family history. Among the most important determinants of colorectal cancer are dietary habits. High-fat, low-fiber diets are associated with an increased risk for colorectal cancer. Diets with a protective effect include those high in vegetables, fruits, fiber, folate, and calcium. [2]

In addition to the risk factors listed above, an infectious cause of colorectal cancer has been suggested. Many bacterial species inhabit the human colon. Some may be friends, and others foes. Friendly colonic bacteria help with digestion, and in return, the colon provides the bacteria a place to live. The presence of friendly bacteria generally goes unnoticed by the host. Other bacteria in the colon may be harmful and are being investigated as potential causes for irritable bowel disease [3] and colorectal cancer. Enteroccocus faecalis (or E. faecalis) is one such bacterium under study for its role in colorectal cancer.

E. faecalis is common and present in most colons. It lives in disease-free individuals as well as people with colorectal cancer. For most, E. faecalis appears to be harmless. But recent studies have shown evidence that E. faecalis is not an innocent bystander in susceptible hosts.[4] The question arises: How could E. faecalis cause cancer in some and be harmless in others?

A characteristic feature of colorectal cancer is genomic instability. Genomic instability refers to chromosomal rearrangement, duplications, and other types of DNA damage. Theories have developed to explain how E. faecalis could contribute to genomic instability. One theory is that E. faecalis produces free radicals such as extracellular superoxide and hydrogen peroxide. Free radicals are highly reactive with other molecules. The free radicals could directly cause mutations in colonic DNA; it is also possible for free radicals to form carcinogens indirectly from dietary procarcinogens (a substance that becomes a carcinogen after being altered). [4]

Results from a study by Huycke et al [3] supports this theory. The investigators found that E. faecalis produces extracellular superoxide and reactive oxygen species capable of causing genomic instability. Free radical production by E. faecalis has the potential to damage DNA in the colon. If production of these free radicals becomes chronic, DNA damage would be ongoing leading to increased genomic instability and mutations. [4]

Dietary risk factors could be combined with the theory about DNA damage induced by E. faecalis to explain some cases of colorectal cancer. An interaction between diet and E. faecalis could also explain why some people develop cancer and others remain disease free. High-risk diets include diets rich in meat and iron. High concentrations of iron in the colon could accelerate formation of free radicals and mutagenic products. Low-risk diets such as those rich in fruits, vegetables and fiber, contain antioxidants that can “round-up” free radicals and reactive oxygen species to limit the potential for DNA damage. Dietary intake could influence the amount and types of carcinogens E. faecalis and other bacteria produce in the colon. Studies are needed to investigate the interaction between infectious causes such as E. faecalis and dietary intake. [5]

The link between colorectal cancer and an infectious agent has been investigated for other bacteria. Streptococcus bovis (S. bovis) has also been linked to colorectal cancer. A case-control study was done to determine the presence of S. bovis in 16 patients with colonic cancer and 16 age matched controls. The presence of E. faecalis was determined by looking for antibodies against E. faecalis. More antibodies often indicate a larger response by the host to bacteria in the body. An increase in antibodies against S. bovis was detected in patients with colonic cancer, but an increase in antibodies against E. faecalis was also seen. In fact, there was a greater increase in antibodies against E. faecalis compared to S. bovis. [5]

There are few epidemiological studies on E. faecalis in colorectal cancer. One study collected stools from patients undergoing colonoscopy who had no prior history of colonoscopy or colorectal cancer. Enterococci were later isolated from the stool samples. Free radical producing enterococci were found in 40 percent of the stool samples. No association was found between colonization with enterococci and colorectal cancer. The study had limitations. The patients were not tracked long enough to study chronic infection and genomic instability that occurs over decades instead of years. In addition, the presence of any enterococci was evaluated instead of focusing on E. faecalis. It is possible that E. faecalis differs significantly from other enterococci in the ability to cause colorectal cancer. [6]

Much remains unknown about the cause of colorectal cancer. Research linking lifestyle factors and infectious causes is lacking. There is a need for more epidemiological studies and studies describing potential pathways leading to the development of cancer. E. faecalis, or any other infectious cause, has not yet been definitively associated with colorectal cancer. Lifestyle factors and family history will remain important risk factors regardless of an infectious cause, but these factors may interact with bacteria found in the colon and help explain why some individuals are at an increased risk for colorectal cancer.

1. Colorectal Cancer Overview. (1999) Colon Cancer (Colorectal Cancer). Retrieved 4/10/2010, from

2. Sandler RS. (1996) Epidemiology and risk factors for colorectal cancer. Gastroenterol Clin North Am; 25(4):717-735.

3. Balish E and Warner T. (2002) Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J of Path; 160:2253-2257.

4. Huycke MM, Abrams V, and Moore DR. (2002) Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis; 23(3):529-536.

5. Darjee R and Gibb AP. (1993) Serological investigation into the association between Streptococcus bovis and colonic cancer. J Clin Pathol; 46:1116-1119.

6. Winters MD, Schlinke TL, Joyce WA, Glore SR, Huycke MM. (1998) Prospective case-control study of intestinal colonization with enterococci that produce extracellular superoxide and the risk for colorectal adenomas or cancer. Am J Gastroenterol; 93(12):2491-2500.

Malignant Mesothelioma and Simian Virus 40 (SV40)

Student guest post by Andrew Behan

Malignant Mesothelioma (MM) is a rare type of cancer which manifests itself in the thin cells lining the human body’s internal organs. There are three types of MM; pleural mesothelioma, peritoneal mesothelioma, and pericardial mesothelioma, affecting the lining of the lungs, abdominal cavity, and lining of the heart, respectively (1). Pleural mesothelioma is most common, consisting of about 70% of all MM cases and has a poor prognosis; patients live a median time of 18 months after diagnosis. (Note: for the purposes of this article, MM will be used to represent pleural mesothelioma exclusively.) Despite its discovery in the mid-1800’s, MM was not linked to asbestos until the late 1900’s, when case reports of fast-growing lung cancers, different from previously described lung cancers, motivated investigators to uncover undisputed evidence linking asbestos to MM. Measures to reduce/eliminate asbestos from buildings reduced exposure to the cancer-causing agents found within the material, and public health officials remained confident by the year 2000 MM cases would decline in the U.S. and parts of Europe. Despite these predictions, MM cases have not declined. In fact, the incidence of MM is on the rise (1). Consequently, investigators have focused their attention on other factors to explain the steady incidence of MM in the U.S., eventually naming Simian Virus 40 (SV40) as a potential cause of MM.

You might be asking, “SV40? What’s that?” SV40 is a virus originally discovered in 1960 in kidney cells of rhesus monkeys. SV40 is dormant and asymptomatic in rhesus monkeys, but was later found to cause kidney disease, sarcoma, and other cancers in animal models. Later on, it was found SV40 attacks p53 gene (a tumor suppressor) and can interrupt the cell’s ability to perform apoptosis, or cell death. This makes the cells immortal, leading to tumor formation, or cancer (2). Controversy arose when the discovery of SV40 was found in the rhesus monkey kidney cells because these same cells were being utilized to form the polio vaccine. Consequently, many polio vaccines were contaminated with SV40 and when the vaccine was used to inoculate humans, SV40 was passed to humans along with the inactive form of the polio virus. It was estimated over 98 million Americans received the vaccine from 1955-1963, when a proportion of the vaccine was contaminated with SV40. Of the 98 million vaccinated during this time period, it was estimated 10-30 million of those individuals were exposed to SV40. Naturally, people who received contaminated forms of the vaccine were afraid they would develop cancer from exposure to SV40.

Since the controversy began in 1960, research has been devoted to confirming its role in cancer development in humans, as well as many animal models. As I mentioned above, presence of SV40 in animals has led to tumors and other cancers, and a few studies have found presence of SV40 in humans who have developed MM. For example, Carbone et al. found SV40 in mesothelial cells of humans who had developed MM, but not in the surrounding tissue (3). They did not find SV40 in patients who had other lung cancers, possibly reinforcing the specificity of their findings (3). Overall, 54% of MM cases were found to have SV40 infection within the mesothelial cells (3). The investigators determined more research needed to be done to see if SV40 infection alone could cause MM, or if other factors, such as immunosuppression or exposure to asbestos, were necessary for development of MM.

Other studies were not as convincing. For example, Lopez-Rios et al. reported that initially they detected SV40 in about 60% of MM specimens, and then they determined that most of the positive results were caused by plasmid PCR contamination, and that only 6% of the initially positive samples were confirmed to contain SV40 DNA (4). However, studies have shown the presence of SV40 in human specimens by using several other techniques besides PCR, including Southern blotting, immunostaining, RNA in situ hybridization, microdissection, and electron microscopy” (5).

Thus, the question remains: does SV40 cause MM, or does SV40 infection, in conjunction with asbestos exposure, generate a greater risk for the development of MM? This is a tough question to answer, because although asbestos is no longer mined in the U.S., it is still being imported; workers are still continually being exposed to asbestos. However, the use of asbestos has nearly ceased, decreasing from 813,000 metric tons in 1973, to 1700 metric tons in 2007 (6). The other problem in teasing out SV40 as a cause of MM from asbestos lies in the latency period between asbestos exposure and MM clinical diagnosis. According to the CDC, the latency period for someone who is first exposed to asbestos and clinical disease is 20-40 years. It may be, given asbestos still remains in many buildings, and exposure to it is inevitable when removal is completed, in addition to the long latency period between exposure and disease, that we have not yet come to the dramatic decrease in MM health officials have predicted. Or, is SV40 infection the culprit and the increase in incidence of MM will continue to rise? According to the SV40 Foundation, “SV40 is a problem that federal government authorities have not addressed responsibly because the government’s own vaccine programs are responsible for the spread of the virus throughout the western world”.(2) It is no question the public has not forgotten, even after almost 50 years, and much more research into this area is needed, to attempt to confirm SV40’s causal role, if any, in the development of MM.


(1) Mesothelioma. Retrieved April 2010.

(2) “Treating SV40 Cancers.” Retrieved April 2010.

(3) Carbone, M. “Simian virus 40 and human tumors: It is time to study mechanisms.” Retrieved from PubMed April 2010.

(4) López-Ríos F, Illei PB, Rusch V, et al. “Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids”. Lancet. 2004;364:1157-1166.

(5) Yang, Haining et al. “Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis.” Retrieved from PubMed April 2010

(6) CDC. “Mesothelioma.” Retrieved from PubMed April 2010.

Alcohol based mouthwash and Oral Cancer – too much confusion

Student guest post by Francis Mawanda

If you are like me, you probably always and almost faithfully, include a bottle of mouthwash on your grocery list especially after watching and/or listening to the numerous commercials in the media which claim that you will not only get long lasting fresh breath, but also freedom from the germs that cause plaque and gingivitis. However, many proprietary mouthwashes including my favorite brand contain Alcohol (ethanol) which also gives them the characteristic burn we have to endure, albeit for a few seconds each day, but safe in the knowledge that the product is hard at work killing all the germs that give us bad breath and may cause plaque and gingivitis. But the question I continually ask myself is whether regular or long term use of these products is safe especially after reading the numerous research reports and newspaper articles suggesting a possible link between long term use of alcohol based mouthwashes and oral cancer.

Several research studies have reported finding an association between long term mouthwash use and oral cancer (1, 2, 3). For example, in a study conducted by Wynder and colleagues (1), they found a significant association between mouthwash use and oral cancer. A bigger multi-site study by Guha and colleagues (3) comparing participants who reported having used mouthwash to those who reported never having used mouthwash found that individuals who reported using mouthwash more than twice a day were nearly six times more likely to develop oral squamous cell carcinoma compared to those who reported never having used mouthwash. However, in both these studies, no distinction was made on whether participants used alcohol or non-alcohol based mouthwashes which raises several epidemiological concerns such as specificity, since not all mouthwashes contain the same chemical ingredients

However, several studies have been conducted in which a distinction was made between alcohol containing and non alcohol containing mouthwash use (4, 5, 6). Unfortunately, these studies have produced mixed results. While some studies reported finding a positive association between alcohol containing mouthwash use and oral cancer (4), other studies found no association at all (5, 6). For example, although a 1983 study conducted in the states of California, Atlanta, and New Jersey by Winn and colleagues (4) found an increased risk of oral cancer among users of alcohol containing mouthwash compared to both non-users and users of non-alcohol based mouthwash, a similar study conducted in Puerto Rico found no significant association between the use of alcohol based mouthwash and oral cancer.

To add to the confusion is the fact that reviews of the subject by epidemiologists and other experts have also produced mixed results. While some researchers in their reviews concluded that the results of these studies provide sufficient evidence to demonstrate a link between long term use of alcohol based mouthwash and oral cancer (7, 8), other researchers concluded that the evidence is not sufficient to make the conclusion that there is an association between alcohol based mouthwash use and oral cancer (9,10).

Furthermore, while systematic reviews or meta-analyses can give us a better picture of the association between use of alcohol based mouthwashes and oral cancer because they can generate a pooled risk estimate by aggregating all the findings on the subject, there has only been one meta-analysis on this subject which was conducted by epidemiologists in Europe (10) and concluded that there is no excess risk for oral cancer from use of alcohol or non-alcohol based mouthwash.

From all this confusion, it’s clear that a randomized control trial (RCT) is needed to determine with a higher degree of certainty whether there is a true association between long term use of alcohol based mouthwashes and oral cancer. However a RCT is not feasible in this case simply because it would be unethical to expose individuals to a product that may cause cancer however weak the association maybe. Possible alternatives include quasi-experimental studies, prospective cohort studies or repeated case-control studies which may provide sufficient evidence through consistency. However, results from these alternatives will still face criticism since they do not offer unbiased estimates.

Therefore, until concrete evidence is available, the decisions on whether to use mouthwash or not and whether to use alcohol based or non-alcohol based mouthwashes remains a matter of personal preference and of course cost for some of us.


1. Weaver A, Fleming SM, Smith DB. Mouthwash and oral cancer: carcinogen or coincidence? Journal of Oral Surgery 1979;37:250-3.

2. Wynder E L, Kabat G, Rosenberg S, Levenstein M.Oral cancer and mouthwash use. J National Cancer Institute 1983; 70: 255-260.

3. Guha N, Boffetta P, Wunsch Filho V et al. Oral health and risk of squamous cell carcinoma of the head and neck and oesophagus: results of two multicentric case-control studies. American Journal of Epidemiology 2007; 166: 1159-1173.

4. Winn D M, Blot W J, McLaughlin J K et al. Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Research 1991; 51: 3044-3047.

5. Winn D M, Diehl S R, Brown L M et al. Mouthwash in the etiology of oral cancer in Puerto Rico. Cancer Causes Control 2001; 12: 419-429.

6. Marshberg A, Barsa P, Grossman M L. A study of the relationship between mouthwash use and oral and pharyngeal cancer. Journal of the American Dental Association 1985; 110: 731-734.

7. McCullough M J, Farah C S. The role of alcohol in oral carcinogenesis with particular reference to alcohol-containing mouthwashes. Aust Dent J 2008; 53: 302-305

8. Werner C .W. & Seymour, R. A., Are alcohol containing mouthwashes safe? British Dental Journal 2009; 207: E19

9. La Vecchia C. Mouthwash and oral cancer risk: an update. Oral Oncology 2009; 45: 198-200.

10. Lewis M A O, Murray S. Safety of alcohol-containing mouthwashes. A review of the evidence. Dent Health (London) 2006; 45: 2-4.

The role of beta-HPVs in skin cancer development

Student guest post by Desiré Christensen

Human papillomaviruses (HPVs) are small DNA viruses that infect epithelial cells. There are well over 100 subtypes of HPV. The subtypes that infect cutaneous epithelia are termed beta-HPVs and those that infect the mucosal epithelia are termed alpha-HPVs. Some alpha-HPVs have received attention as strong risk factors for the development of cervical cancer. Less public awareness has been generated over the role of HPVs in the development of other cancers such as vulvar, vaginal, anal, head and neck, and penile cancers. Only recent research has focused on an association between HPV infection and skin cancer development.

Infection with beta-HPVs and development of skin cancer was first identified in patients with a rare inherited disorder called epidermodysplasia verruciformis (EV)(1). Roughly 50 percent of EV patients develop premalignant skin lesions and squamous cell carcinomas (SCCs) by the time they are 40 (2). Lesions and carcinomas mainly develop in sun-exposed regions, but HPV DNA has also been detected.3 Based on these findings, an interactive carcinogenesis between HPV and UV radiation has been suggested.

Immunocompromised patients are at increased risk of developing SCCs and other skin lesions, supporting the hypothesis that an infectious agent may play a role in skin cancer development. Organ-transplant recipients are at increased risk of developing warts and other skin lesions often followed by the development of SCC. The prevalence of beta-HPV DNA nears 100 percent in premalignant lesions and SCC in these immunocompromised individuals (4,5). In comparison, beta-HPVs have been detected in 30 to 60 percent of SCCs from immunocompetent patients (6).

A study by Karagas et al (7) aimed to describe the association between beta-HPVs and squamous cell carcinomas by testing for anti-HPV antibodies. Anti-HPV antibodies were found 60 percent more often in cases of squamous cell carcinomas compared to controls. A significant association between basal cell carcinoma and beta-HPVs was not observed. Beta-HPVs were associated with squamous cell carcinomas even after adjusting for smoking, drinking, medical and family history, and sun exposure (7).
Mechanisms for the role of HPVs in skin cancer are currently under investigation.

Recent research supports the biologic plausibility of a causal pathway from HPV infection to the development of skin cancer. The E6 and E7 proteins in high-risk types of HPV are known to modify and interact with cellular proteins leading to uncontrolled cell growth. In response to UV damage, the E6 protein from several beta-HPVs effectively inhibits cell apoptosis (8). The promoter of beta-HPV types 5 and 8 is also stimulated by UV exposure (9). Disruption of UV-induced thymine dimer repair has been demonstrated in cells expressing beta-HPV type 5 E6 protein, but has not been shown in cells expressing the E6 protein from other beta-HPVs (10).

The interaction between E6 and Bak, a proapoptotic effector, has been studied as a possible oncogenic pathway. Bak is degraded by the beta-HPV E6 protein resulting in protection from apoptosis in UV damaged cells. The degradation of Bak by beta-HPVs can occur without affecting regulators of Bak. The ability of the E6 protein to degrade Bak was not different between beta-HPV subtypes, suggesting other mechanisms should be studied to explain differential carcinogenesis (11).

More mechanistic studies are needed to determine the carcinogenic properties of beta-HPVs and their potential role in skin cancer development. More epidemiologic studies are needed to determine causality. Most studies have demonstrated an association between beta-HPVs and skin cancer through detection of HPV antibodies or DNA in cancer tissue and the sample sizes used have been small. The presence of HPVs in cancer tissue encourages further investigation but does not prove causation.
UV exposure is known to be a strong risk factor for the development of skin cancer, but recent research has indicated a potential role of HPV infection in skin cancer. It is possible that HPV interacts with UV exposure in oncogenic pathways. There is increasing evidence supporting the biologic plausibility of an interactive effect. Beta-HPVs are ubiquitous in the population and present in both normal and cancer tissues, making it difficult to conduct a prospective study. HPV detection methods have improved over time and should be combined with a strong epidemiologic study design to demonstrate causation (6).


1. Lutzner, M. A., C. Blanchet-Bardon, and G. Orth. (1984) Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses. J Invest Dermatol 83:18-25

2. Orth, G., S. Jablonska, M. Jarzabek-Chorzelska, S. Obalek, G. Rzesa, M. Favre, and O. Croissant. (1979) Characteristics of the lesions and risk of malignant conversion associated with the type of human papillomavirus involved in epidermodysplasia verruciformis. Cancer Res 39: 1074-82

3. Pfister, H. (1992) Human papillomaviruses and skin cancer. Semin Cancer Biol 3:263-71

4. Bouwes Bavinck JN, Plasmeijer EI, Feltkamp MC. (2008) Beta-papilloma- virus infection and skin cancer. J Invest Dermatol 128:1355-8

5. Pfister H. (2003) Human papillomavirus and skin cancer. J Natl Cancer Inst Monogr 31:52-6.

6. Asgari MM, Kiviat NB, Critchlow CW, Stern JE, Argenyi ZB, Raugi GJ et al. (2008) Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals. J Invest Dermatol 128:1409-1417

7. Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A et al. (2006) Human Papillomavirus Infection and Incidence of Squamous Cell and Basal Cell Carcinomas of the Skin Journal of the National Cancer Institute 98:389-395

8. Jackson, S., and A. Storey. (2000) E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage. Oncogene 19:592-8

9. Akgul, B., W. Lemme, R. Garcia-Escudero, A. Storey, and H. J. Pfister. (2005) UV-B irradiation stimulates the promoter activity of the high- risk, cutaneous human papillomavirus 5 and 8 in primary keratinocytes. Arch Virol 150:145-51

10. Giampieri, S., and A. Storey. 2004. Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18. Br J Cancer 90:2203-9

11. Underbrink MP, Howie HL, Bedard KM, Koop JI, and Galloway DA. (2008) The E6 proteins from multiple beta HPV types degrade Bak and protect keratinocytes from apoptosis after UVB irratiation. J Virol 82:10408-17

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