Biomedical & Life Sciences, Faculty of Health & Medicine, Lancaster University, Lancaster LA1 4YQ, United Kingdom.
University Hospitals of Morecambe Bay NHS Trust, Education Department, Royal Lancaster Infirmary, Lancaster LA1 4RP, United Kingdom.
Med Hypotheses. 2020 Mar;136:109530. doi: 10.1016/j.mehy.2019.109530. Epub 2019 Dec 13.
The hierarchical model of stem cell genesis is based on the idea that the number of cell divisions between the zygote and fully differentiated epithelial cells is kept close to the minimum, which is log to the base 2 of the total number of cells produced in a human lifetime. The model assumes the orderly progression of stem cell divisions requires precise control at every stage in development. If the orderly progression is maintained then cancer will be rare. A prediction of the model is that if the orderly progression of the stem cell hierarchy is disturbed by trauma, ulceration or inflammation then cancer will occur.
Bacterial induced inflammation in breast ducts disturbs the stem cell hierarchy and is a cause of breast cancer.
Mammalian milk is not sterile. It contains a range of bacteria, derived endogenously by the entero-mammary circulation. The dominant flora consists of lactose fermenting bacteria. Pregnancy and breast feeding reduce the risk of subsequent breast cancer. The implication is that a lactose fermenting bacterial flora in breast ducts is protective. Malignant and benign breast tissue contains bacteria derived endogenously, but studies so far have not revealed a specific flora associated with malignancy. Periodontitis is associated with oral, oesophageal, colonic, pancreatic, prostatic and breast cancer. The pathogenic bacteria which cause periodontitis spread endogenously to cause inflammation at other epithelial sites. Meta-analysis of epidemiological studies shows that the consumption of yoghurt is associated with a reduction in the risk of breast cancer.
The hypothesis, although not proven, is supported by the available evidence. Lactose fermenting bacteria protect but pathogenic bacteria which induce inflammation raise the risk of breast cancer. The consumption of yoghurt also appears to be protective.
干细胞发生的层次模型基于这样一种理念，即从受精卵到完全分化的上皮细胞之间的细胞分裂次数接近最小值，该最小值是以 2 为底的人类一生中产生的细胞总数的对数。该模型假设干细胞分裂的有序进展需要在发育的每个阶段都进行精确控制。如果有序进展得到维持，那么癌症将很少发生。该模型的一个预测是，如果乳腺导管中的细菌诱导炎症扰乱了干细胞层次结构，那么癌症就会发生。
乳腺导管中的细菌诱导炎症扰乱了干细胞层次结构，是乳腺癌的一个病因。
哺乳动物的乳汁并非无菌，它含有一系列细菌，这些细菌源自肠乳循环的内源性。优势菌群由乳糖发酵细菌组成。怀孕和哺乳会降低随后发生乳腺癌的风险。这意味着乳腺导管中的乳糖发酵细菌菌群具有保护作用。恶性和良性乳腺组织中都含有源自内源性的细菌，但迄今为止的研究尚未揭示出与恶性肿瘤相关的特定菌群。牙周炎与口腔、食管、结肠、胰腺、前列腺和乳腺癌有关。引起牙周炎的致病性细菌会在体内扩散，引起其他上皮部位的炎症。对流行病学研究的荟萃分析表明，酸奶的摄入与乳腺癌风险降低有关。
虽然该假说尚未得到证实，但现有证据对此提供了支持。乳糖发酵细菌具有保护作用，但引起炎症的致病性细菌会增加乳腺癌的风险。酸奶的摄入似乎也具有保护作用。
