PNAS: Not fragrant anymore?

In 2008, Harald zur Hausen won the Nobel Prize podium for his research on human papillomavirus (HPV) and cervical cancer.

In his award speech, the scholar who has explored cancer-causing viruses throughout his life narrated the known relationship between human viruses and cancer, and put forward a new hypothesis at the end-a large number of epidemiological reports found that edible red Meat is related to bowel cancer, breast cancer, and lung cancer in non-smokers, so there may be a hitherto unidentified source of infection from cattle that plays a role in it.

In fact, eating red meat and the increased risk of cancer can be regarded as clichés.

An explanation that is often used is that red meat produces carcinogenic N-nitroso compounds, heterocyclic amines, and heterocyclic aromatic hydrocarbons during the cooking process.

But this is somewhat unreasonable, because white meat also produces these substances after cooking (even the concentration is similar), that makes no sense, only red meat shows "harmful".

Reminiscent of the cooking methods of red meat are often "half-baked", combined with the research experience on other carcinogenic pathogens, zur Hausen would suspect the existence of unknown bovine pathogens, which is very reasonable.

In Western-style cooking, beef is often "cooked" | pixabay is less than ten years old, this hypothesis has been confirmed.

The team of Zur Hausen and another scientist, Ethel-Michele de Villiers, examined the blood serum of hundreds of cows and large quantities of milk and dairy products purchased from supermarkets, and discovered a potential new type of pathogen—not a virus— —Single-stranded circular DNA with high homology to bacterial plasmids.
They are named Bovine Meat and Milk Factors (BMMF).

BMMF carries a gene encoding the replication initiator protein (Rep protein), which has characteristics between viruses and bacteria, and has high homology with plasmids from Acinetobacter baumannii.

So far, scientists have discovered more than 120 different BMMF sequences in bovine serum, milk, and dairy products.

Recently, the scientific research team published new research results in the journal Proceedings of the National Academy of Sciences.
They found through immunohistochemical analysis that the presence of BMMF can induce chronic inflammation and thereby increase the level of oxidative stress.
This leads to gene mutations, which promotes the occurrence of colorectal cancer for a long time.

In this study, the researchers established a series of monoclonal antibodies against the Rep protein of BMMF1, a subgroup of BMMF in mice, and used these antibodies to analyze surgically resected samples from patients with colorectal cancer.

Among 16 cases of colorectal cancer tissue, 15 cases were positive by Western blot (WB) analysis, and 4 cases of colon adenoma (polyp) tissue were also positive.

Interestingly, immunohistochemical analysis (IHC) of tissue sections adjacent to cancer also detected positive staining, and the researchers also isolated DNA fragments of BMMF.

Further immunofluorescence (IF) analysis revealed that the presence of BMMF antigen is consistent with CD68+ macrophages, but lacks T cells and B cells.

This indicates that BMMF-infected tissues are likely to exhibit a chronic inflammatory phenotype driven by macrophages.

Chronic inflammation is complicated.
Its appearance is often closely related to the formation of oxygen free radicals, cell stress, and nucleic acid repair defects.

Sure enough, the researchers observed positive staining of 8-OHdG in tissues with higher levels of Rep protein, which is a product of DNA oxidation by reactive oxygen species and reactive nitrogen free radicals.

Signs of oxidative stress were found in tissues with high Rep levels.
Researchers also compared Rep/CD68 combined signals in colorectal cancer samples and cancer-free control tissue samples, and found that 7.
3% of intestinal cells in the tumor environment were Rep/CD68 positive.
In the control group, it was only 1.
7%.

These local inflammations appear near the intestinal crypts, the hometown of intestinal stem cells.

It is conceivable that the presence of BMMF induces gene mutations in the rapidly renewing intestinal stem cells through chronic inflammation and oxidative stress, and cancer may occur in this way.

Therefore, the researchers believe that BMMF can be regarded as an indirect carcinogen.
The results of this study support the causal relationship between milk and beef consumption and the development of colorectal cancer.
It also suggests that the detection of BMMF may be an early colorectal cancer.
An indicator of cancer screening.

Can milk and beef still be eaten? According to the previous research results of the research team, we are now worried that this may be a bit late.
.
.
Previous research results believe that BMMF infection is most likely to occur after the baby is born and weaned to before the immune system matures.
Avoid milk and beef during adulthood.
There is almost no effect.

According to zur Hausen, vaccinating babies or cattle may be a more reliable method.

But we Asians seem to be less worried.

After analyzing a number of studies around the world, Professor zur Hausen’s team found that North America, Argentina, Europe and Australia use a large amount of beef and dairy products from European cattle.
These areas have a higher incidence of colorectal cancer and breast cancer; However, the incidence rates in Mongolia, Bolivia and India are relatively low, and Asian zebu is the main food in these areas.

In the two European cattle on the right, the risk of breast cancer in parts of BMMF India is increasing.
Data from Japan and South Korea also show that the risk of colorectal cancer has increased significantly, which may be related to imported beef and beef products from Europe.

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 Reference materials: [1] beef-and-cows-milk-contributing-to-the-risk-of-cancer[3] Zur Hausen H, Bund T, de Villiers EM: Specific nutritional infections early in life as risk factors for human colon and breast cancers several decades later.
Int.
J.
Cancer 144, 1574-1583 (2019).
DOI: 10.
1002/ijc.
31882[5] Eilebrecht S, Hotz -Wagenblatt A, Sarachaga V, Burk A, Falida K, Chakraborty D, Nikitina E, Tessmer C, Whitley C, Sauerland C, Gunst K, Grewe I, Bund T: Expression and replication of virus-like circular DNA in human cells.
Scientific Reports 8: 2851 (2018).
DOI: 10.
1038/s41598-018-21317-w[6] Zur Hausen H, Bund T, de Villiers E.
-M.
:Infectious agents in bovine red meat and milk and their potential role in cancer and other chronic diseases.
Current Topics in Microbiology and Immunology 407, 83-116 (2017).
DOI: 10.
1007/82_2017_3