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

Yoghurt and Risk of Proximal Colorectal Cancer

A systematic review and meta-analysis revealed that the frequency of yogurt consumption was associated with a reduced risk of proximal colon cancer with a long latency period (4):

• In this study it was commented that "..the stronger association of proximal colon cancer with yogurt consumption at baseline observed in our study may reflect the longer latency period, relevant for the cancer of this site in its multistage process. Indeed, our latency analyses point towards a 16–20-year latency for the association between yogurt consumption and overall CRC incidence..."

A study investigated the consumption of yoghurt and incidence of Bifidobacterium-positive colorectal cancer (5):

• evidence indicates that probiotics such as yogurt may play a cancer-preventative role via their effect on the intestinal microbiota composition and/or intestinal barrier function.
  • among important probiotic bacterial strains in yogurt, Bifidobacterium is suggested to have a tumor-suppressive effect
• tested the hypothesis that the association of long-term yogurt intake with colorectal cancer incidence might differ by the abundance of tumor tissue Bifidobacterium
• the study authors hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue Bifidobacterium
  
  • previous study evidence showed that Bifidobacterium-positive colorectal cancer was associated with signet ring cell histology but not with other tumor characteristics or prognosis in colorectal cancer patients
  • the link between tissue Bifidobacterium abundance and the signet ring cell feature potentially implies that loss of epithelial cellular adhesion (observed in signet ring cells) might cause the entry of Bifidobacterium into colonic tissues
  • other study evidence study also suggests that tumor Bifidobacterium might be an indicator of dysfunctional intestinal barriers in colorectal cancer
    
• Ugai et al observed such a differential association, especially for proximal colon cancer, with a trend of the association of yogurt intake with lower incidence of Bifidobacterium-positive proximal colon cancer (but not Bifidobacterium-negative subtype)

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)
4. Sun J et al . Higher Yogurt Consumption Is Associated With Lower Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Observational Studies. Front Nutr. 2022 Jan 3;8:789006.
5. Ugai, S et al. Long-term yogurt intake and colorectal cancer incidence subclassified by Bifidobacterium abundance in tumor. Gut Microbes 2025; 17(1)