Bovine Meat and Milk Factors (BMMFs) and cancer

Bovine Meat and Milk Factors (BMMFs) and cancer

• epidemiological studies have pointed to a relationship between colon, breast and prostate cancers and nutritional habits - especially with reference to red meat consumption (1)
  • countries consuming red meat mostly from Eurasian dairy cattle origins revealed high incidences of breast and colon cancers
  • an exception is Mongolia
    • residents of this country traditionally consume high quantities of red meat (from Yak or Chinese Yellow cattle origin), but incidences of colon and breast cancers are very low
      • studies show differences in cancer risk involving consumption of red meat originating from different species of cattle, e.g., Eurasian dairy cattle versus Zebu and Yak breeds
  • a correlation of high (adult) milk consumption with increased cancer risk has already been reported for cancers like breast, lung and prostate cancer (2)
    
    
• BMMFs
  • are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients (2)
  • have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage (2)
  • BMMF Rep (replication protein) expression is associated with an increased number of M2-like macrophages
  • Nikitina et al showed:
    • BMMF Rep (replication protein) expression was localized primarily in M2-like interstitial macrophages of the tumor-adjacent mucosa of CRC patients, while significantly less Rep expression was observed in the tumor and healthy controls, the latter underlining an association of BMMF with CRC
    • link of high tumor-adjacent Rep expression with increased CRC-specific death suggests a contribution of BMMF on patient prognosis even after tumor resection

Calcium intake as a protective factor in colorectal cancer:

A prospective study of more than half a million UK women conducted over almost 17 years showed (3):

• research team, led by the University of Oxford, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years
  • during this period 12,251 participants developed colorectal cancer
  • calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR (relative risk)
    • six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk
    • alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase
      • weaker associations were seen for the combined category of red and processed meat, with each additional 30 g/per day associated with an 8% increased RR for colorectal cancer
  • study authors concluded that dairy products help protect against colorectal cancer, and that this is driven largely or wholly by calcium

Reference:

1. de Villiers EM, Zur Hausen H. Bovine Meat and Milk Factors (BMMFs): Their Proposed Role in Common Human Cancers and Type 2 Diabetes Mellitus. Cancers (Basel). 2021 Oct 28;13(21):5407. doi: 10.3390/cancers13215407.
2. Nikitina E, Burk-Korner A, Wiesenfarth M, Alwers E, Heide D, Tessmer C, Ernst C, Krunic D, Schrotz-King P, Chang-Claude J, von Winterfeld M, Herpel E, Brobeil A, Brenner H, Heikenwalder M, Hoffmeister M, Kopp-Schneider A, Bund T. Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival. Mol Oncol. 2023 Feb 22. doi: 10.1002/1878-0261.13390.
3. Papier, K., Bradbury, K.E., Balkwill, A. et al. Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK. Nat Commun16, 375 (2025)