Harald zur Hausen, former long-standing chairman of the board of the German Cancer Research Center (DKFZ) in Heidelberg, received the Nobel Prize for Physiology and Medicine in 2008 for his discovery that cervical cancer is caused by human papillomaviruses (HPV). In his Nobel Lecture on 7th December 2008, zur Haussen stressed that he did not think that cervical cancer was the only cancer caused by viruses. He also said that slightly more than 20% of the global cancer burden is linked to viral and bacterial infections. Zur Haussen calls viruses causative factors for human cancers; he does not like to use the word "cause" because the development of cancer is down to many rather than just one cause. Moreover, the infectious agents can have a direct or indirect effect on the transformation of healthy cells into cancer cells. 

In addition to the 500,000 or so cases of cervical cancer per year worldwide, human papillomaviruses are also responsible for around 70,000 cancers of the oral cavity. Hepatitis B and C viruses are involved in the development of an estimated 80% of all cases of highly malignant hepatocellular cancer. Infections with the bacterium Helicobacter pylori, which lives in the human gastric tract, have also been identified as causes for around 80% (approx. 750,000 cases) of all stomach cancers in the world. In addition, over 90,000 cases of stomach cancers are attributable to Epstein-Barr virus infections.

In addition to these common cancers, viruses have also been identified as risk factors in a number of lesser-known cancers, including Kaposi's sarcoma, Merkel cell carcinoma and nasopharyngeal carcinoma. As zur Hausen pointed out at the Nobel Laureate Meeting in Lindau in 2014, he believes that the development of two of the most frequent cancers (colorectal carcinoma and breast cancer) can best be explained by infectious factors such as viruses. His thesis that the agents transferred to humans on consumption of beef and dairy products are viruses caused quite a stir. 

Together with his wife Professor Ethel-Michele de Villiers and his team in the DKFZ department "Episomal-persisting DNA in cancer and chronic diseases", zur Hausen isolated numerous novel episomal DNA sequences from the meat and serum of healthy dairy cows. These sequences show a close relationship with circular, single-stranded DNA viruses. Some of these viruses have been shown to infect human cells. Homologous sequences isolated from human tissue or serum suggested beef consumption as a potential transmission route. Numerous studies have shown that the consumption of red meat and meat products increases the risk of developing and dying from colorectal cancer. Carcinogens (in particular polycyclic aromatic hydrocarbons and nitrosamines) produced during the cooking, broiling, barbecuing and processing of red meat were initially suggested as the causative agents of colorectal cancer.

However, Harald zur Hausen stressed that fried, grilled or smoked chicken and fish meat contains equally high concentrations of chemical carcinogens, but that these meats have not been found to be associated with an elevated risk of colorectal cancer. Apparently, the risk factor is not red meat in general, but rather cattle meat that is raw or inadequately cooked. The Nobel Laureate showed that many potentially carcinogenic viruses retain infectious properties even at temperatures of over 70 °C; inside a "medium" or "rare" beef steak, the temperatures are always significantly lower than this.

In studies on colorectal cancer in Japan and South Korea, zur Hausen found that the two countries, which previously had a low incidence of colorectal cancer, are now, along with Australia, Canada and the USA, among the countries with the highest rates of colorectal carcinoma. In Japan, the number of people dying from colorectal cancer more than doubled between 1975 and 1997. A similar increase was observed in Korea twenty years later. With Korea and Japan opening up to the American market, imports of beef, pork and dairy products from cattle grew enormously in the 1970s. Koreans and Japanese like to eat their beef undercooked or rare. This is in stark contrast to Saudi Arabia where the consumption of cattle beef has also increased considerably, but where steaks are preferred "well-done". The incidence of colorectal cancer in Saudi Arabia is therefore relatively low. Mongolia, where a lot of meat is consumed, including raw as a type of tartare, also has a low colorectal cancer rate, which zur Hausen suggested is due to the Mongolian custom of eating mainly mutton, goat and yak (Bos mutus). The latter is different from domestic cattle (Bos taurus), and is not thought to transmit potential cancer-causing viruses to humans.

The analysis of published epidemiological data on colon cancer and breast cancer reveals a remarkable concordance for most regions of the world. This might be due to similar risk factors. In their most recent publication, zur Hausen and de Villiers described DNA sequences of viral origin which they discovered in the milk of healthy cows, and which had a high degree of homology with human tissue isolates. These findings, together with epidemiological analyses, suggest that the consumption of (Bos taurus) milk and milk products at an early stage in life is one of the major risk factors for the development of breast cancer. India, which is the largest milk producer in the world, but has an exceptionally high number of vegetarians, has a high incidence of breast cancer, but a relatively low rate of colon cancer. Another recent study showed that individuals with lactose intolerance who had consumed only small amounts of cow's milk, had a reduced risk of developing breast cancer. And this effect was not due to the families' genetic make-up.

Of course, Harald zur Hausen does not doubt the importance of genetic factors in the development of cancer. Virtually all infections that lead to tumours in humans depend on modifications in certain signalling chains of the host cell or specific oncogene mutations. These modifications are facilitated by chemical and physical carcinogens. Viral infection by way of cattle meat or cow's milk would be an essential factor for the development of cancer. However, there are good reasons to assume that chemical carcinogens have synergistic (not necessarily synchronous) effects. In his lecture at the Nobel Laureate Meeting in Lindau, Harald zur Hausen, adopted a subtly ironic approach by confronting the accepted idea that cancer is a genetic dysregulation: "The common idea is that human cancer develops due to an imbalance between proto-oncogenes and tumour suppressor genes. Cancer-causing viral infections disturb this wonderful picture."

References:

zur Hausen H, de Villiers EM: Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers. Int J Cancer. 2015 Feb 3.doi: 10.1002/ijc.29466

zur Hausen H, de Villiers EM: Cancer "causation" by infections – individual contributions and synergistic networks. Seminars in Oncology. 2014, 41(6): 860-875

zur Hausen H: Red meat consumption and cancer: Reasons to supect involvement of bovine infectious factors in colorectal cancer. Int J Cancer: 130.2475-2483 (2012)