Viruses, red meat consumption and cancer

As reported in The Times of London on Saturday March 8th 2019, researchers are dismissing the link between the increase in beef consumption to the increase seen in colorectal cancer in the developed world.

The potential link between cancer and the consumption of red meat is no new - first reports published in 1977 linked the formation of carcinogenic polycyclic aromatic hydrocarbons and derivates of nitrosamine during processing of red meat in particular barbecuing and broiling as a risk factor for cancer. Early studies however indicated that consuming poultry or fish does not carry the same risk.

Epidemiological studies however revealed that the increased risk for red meat seems to be restricted to populations with a high consumption of beef, but virtually absent in countries in which beef consumption is low such as India or the Arabic countries. Indeed the ethnic Indian and Pakistani in England and Wales has the lower incidence rate of colorectal cancer compared to the rest of the population. Similar results have been reported from Singapore and the US, suggesting that the dietary restrictions laid down in religious rules play an important role in the prevention of colorectal cancer (it should be noted however that they have an increased risk of other cancers such as gall bladder cancer and laryngeal cancer in males). In India the exception is the state of Kerala, which has a high proportion of Christian and Muslim populations.

So far so good, where is the link to viruses? Viruses are well known to be a causative agent for a variety of cancers in humans and animals alike. One of the most examples is surely Human Papillomavirus, the causative agent of cervical and penile cancer (among others), Kaposi Sarcoma Herpesvirus, the causative agent of melanoma particularly in HIV positive patients and Epstein Barr Virus, the causative agent of Burkitts Lymphoma in wide parts of the African continent. The first virus causing cancer was identified however in chicken - Rous Sarcoma Virus. It is also known that meat can transfer diseases to humans - indeed there is some speculation that the dietary laws laid down in the Torah were enforced precisely to prevent the transmission of parasitic diseases. 

Evidence of an infectious agent wing involved in the onset of colorectal cancer comes from detailed epidemiological studies, comparing data from South Korea and Japan. Japan -traditionally known for its high consumption of seafood- shifted towards a beef dominated diet in the 1970s. From 1975 onward a rapid increase in colorectal cancer can be observed with numbers decreasing in the last years - the latter coinciding with a decrease in beef imports from the US. Korea on the other hand did not see an increase in colorectal cancer before 1995, coinciding with an increased popularity for beef and dairy products. Other countries such as Australia, Canada and the US are seeing decreased rates probably because more and more consumers decrease meat consumption for health reasons, in particular obesity and cardiovascular disease. 

Still this does not prove a link between viruses or other pathogens and colorectal cancer. In both Korea and Japan however beef is served undercooked, a link supported by observations that in Saudi Arabia that the increased consumption of beef is (so far) not linked to an increase cancer risk (here beef is served well-done). 

What about viruses? Rather than causing cancer per se, viruses might play an auxiliary role, similar to the development of Epidermodysplasia verruciformis, a hereditary form of skin cancer, where HPV types 5 and 8 are contributing factors of the disease. In this scenario, viral infection would cause a transient or latent infection which -together with inherited genetic modifications and other risk factors such as nitrosamines- would lead to the developing of colorectal (and maybe other) cancers. The viral agents are however have not been identified. Early candidates included Human or Bovine Papillomavirus but failed detection. Another group included TT virus, but again so far no conclusive evidence has been reported. The possibility of an unknown (animal) virus is not so far fetched since it has been reported that the human variant of Hepatitis C virus derived from a canine variant approximately 500-100 years ago. 

It should also be noted that Torquetenovirus  (TT) virus, although being found in colorectal tumor tissue,  is acquired by in utero infections  and prevalent in 80% of the world population. Since TT virus induces a pro-inflammatory response via Toll-like receptor-9 activated pathways, it is conceivable that this activity might contribute tot he pathogenesis of the disease. It should be noted that TT viral DNA has also been detected in bone marrow and peripheral blood mononuclear cells from cancer patients.

What is the final assessment? While the majority of researchers are dismissing the link between meat consumption and colorectal cancer a minority -in particular Harald zur Hausen- believes that viruses can be at least a contributor in the onset of various cancers. Those who follow the Paleo-diet advocate to eat meat from grass-fed cattle and free-range chicken. The answer in the end might be in the grey area of science, where undercooked meat contaminated with pathogens (either viruses or bacteria) in combination with genetic factors of the individual might be a contributing factor in the onset of colorectal cancer. Excess meat consumption plays an important role in the development of heart disease and obesity. So should we decrease the amount of meat in our diet? Absolutely! But leave the viruses out of the story.

Further reading:

Xu B, Sun J, Sun Y, Huang L, Tang Y, & Yuan Y. (2019) No evidence of decreased risk of colorectal adenomas with white meat, poultry, and fish intake: a meta-analysis of observational studies. Annals of epidemiology, 23(4), 215-22. PMID: 23375344

Egeberg R, Olsen A, Christensen J, Halkjær J, Jakobsen MU, Overvad K, & Tjønneland A. (2019) Associations between red meat and risks for colon and rectal cancer depend on the type of red meat consumed. The Journal of nutrition, 143(4), 464-72. PMID: 23427329

zur Hausen H. (2012) Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. International journal of cancer. Journal international du cancer, 130(11), 2475-83. PMID: 22212999

Berjia FL, Poulsen M, & Nauta M. (2019) Burden of diseases estimates associated to different red meat cooking practices. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 237-244. PMID: 24491261

zur Hausen H. (2012) Q&A: On the case. Interview by Michelle Grayson. Nature, 488(7413). PMID: 22932436

de Villiers EM, Bulajic M, Nitsch C, Kecmanovic D, Pavlov M, Kopp-Schneider A, & Löhr M. (2007) TTV infection in colorectal cancer tissues and normal mucosa. International journal of cancer. Journal international du cancer, 121(9), 2109-12. PMID: 17620330

Rocchi J, Ricci V, Albani M, Lanini L, Andreoli E, Macera L, Pistello M, Ceccherini-Nelli L, Bendinelli M, & Maggi F. (2009) Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9. Virology, 394(2), 235-42. PMID: 19765789