13. How the first seeds of the monster of cancer develop.
3000 years ago, a stocky man named Ethred crouched in the woods of England. The other members of his tribe were in the distance, as they had spotted a boar earlier. The group agreed to split up, and half of them circled behind the boar. They were now hollering, to scare the boar down the ravine toward Ethred and his brother. Suddenly, a boar came bolting out of the forest. He and his brother yelled at the startled animal, held their spears and charged in for the kill. The boar swung his snout, its’ tusk gouging Ethred’s arm that held the spear. Ethred’s brother pinned the boar to the ground with his spear, and Ethred ignored the pain to plunge his spear into the boar’s heart.
A second attack started immediately, and it was vastly more complex than a tribe splitting into two groups to hunt a boar. The damaged cells on Ethred’s skin released various chemical signals, which included cytokines.[i] These made the blood vessels dilate and the area around the wound became red and swollen. They also signaled the immune system to get into action. White blood cells attacked the foreign bacteria that had been living on the boar’s tusk. Other chemical signals indicated pain, so that Ethred protected his arm from further damage. The cytokines and some of the white blood cells signalled the cells in the area to proliferate, so that they could rebuild the tissue that had been torn. Dead cells were cleaned up, and the various layers of cells communicated with each other to rebuild the damaged tissue and send blood vessels in to nourish the new tissue. Within a few weeks, the wound had largely healed and the body was back in equilibrium. This process is known as inflammation. It involves sophisticated chemical signals from damaged cells, the immune system, and blood cells. Inflammation helped stop the infection and kept Ethred alive after the injury. He went on to have four children.
Millenia later, one of Ethred’s super great-grandsons also crouched down as he heard his kin screaming with maximum effort. His name was Shawn, he was 7 years old, and he was in his bedroom in America. Shawn was hugging his younger sister. The hollering was his father raging against his mother. The insults and screams stabbed into his ears and it felt like his brain was on fire. This was the third night this week that he had to endure it. Abruptly, the door blew open and his father was yelling at him about whether Mom saw another man. Fear paralyzed Shawn’s body, and he shook and stared. He could smell the whisky on his Dad. The truth was, he had seen Mom hug another man in the parking lot, but Shawn was terrified of getting another beating from either parent. His mother screamed at his father to leave the kids alone and pulled her husband out of the room. The storm moved down the hallway, the thumps and insults making Shawn and his sister shake.
These repeated Adverse Childhood Experiences of domestic violence, parental alcoholism and physical and emotional abuse shaped Shawn’s body and brain. Because Shawn went into the fight or flight response so often in childhood, this caused the three glands that control the stress response (hypothalmus, pituitary, and adrenal) to respond abnormally.[ii] Even many years later, when Shawn experienced stress, he had a much stronger response to it than people who had no emotional wounds from their childhood.[iii] [iv] This response included an inflammatory reaction.[v] People that experience ACE’s in childhood have higher levels of inflammatory markers in adulthood. These cytokines are the same ones that were released in Ethred’s arm, millenia earlier. They signal the immune system to go into inflammation, and there are a variety of them (Interleukin-6, C-Reactive Protein, and Tumor Necrosis Factor). There even are modifications to the genes (NR3C1 and FKBP5) that regulate how much of these cytokines to produce.[vi] With the genes being altered, then the body is less able to regulate these pro-inflammatory cytokines. The cells are hard-wired to produce more of these cytokines. The result is that inflammation lasts for many years among people with multiple ACE’s. We saw above that inflammation was helpful for Shawn’s super great-grandfather, Ethred, in recovering from the wound from the boar’s tusk. But having too much of a good thing can turn bad.
When inflammation persists year after year, a dangerous situation can develop. If there is a situation that starts a cell on the path to cancer (being exposed to smoke, genetice mutation, etc), the reaction of the immune system may not stop it. [vii] After all, the cell is part of the body, so the immune system recognizes it as friendly. However, the extra cytokines will signal the cells to proliferate. Unfortunately, instead of telling healthy cells to proliferate after an injury, they are telling tumour cells to reproduce faster. The cytokines will also suppress the immune system around the new tumour cells, which allows it to grow. There is now a vast literature showing that when people are in chronic inflammation, that they have a higher incidence of tumours, the tumours grow faster, and they progress more rapidly through the stages to be Stage 4 cancer.
This is one of the pathways for Adverse Childhood Events to increase the risk for cancer later in life. The repeated trauma in childhood alters the stress response, so that the person has higher levels of inflammation through their life. If a cell starts down the pathway to become cancerous, the signals from the cytokines tell it to proliferate faster, and suppress the immune system around the tumour, and tell blood vessels to go to the tumour. This is just an outline of a very complex process, but the dynamic is clear.
Thankfully, there also is a path to intervene. Just because inflammation is chronic, does not mean it is irreversible. The next post will explore a very surprising psychological dynamic to change your body’s level of inflammation. It is effective, and has no negative side effects. Subscribe to learn more.
[i] Greten FR, Grivennikov SI. (2019). Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. Jul 16;51(1):27-41. doi: 10.1016/j.immuni.2019.06.025. PMID: 31315034
[ii] Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, Nemeroff CB. (2000) Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. Aug 2;284(5):592-7. doi: 10.1001/jama.284.5.592. PMID: 10918705
[iii] Janusek LW, Tell D, Gaylord-Harden N, Mathews HL. (2017). Relationship of childhood adversity and neighborhood violence to a proinflammatory phenotype in emerging adult African American men: An epigenetic link. Brain Behav Immun. Feb;60:126-135. doi: 10.1016/j.bbi.2016.10.006. PMID: 27765646
[iv] Childhood maltreatment predicts adult inflammation in a life-course study. (2007). Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Proc Natl Acad Sci U S A. Jan 23;104(4):1319-24. doi: 10.1073/pnas.0610362104. PMID: 17229839
[v] Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. (2016), Childhood trauma and adulthood inflammation: A meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. May;21(5):642-9. doi: 10.1038/mp.2015.67. PMID: 26033244; PMCID: PMC4564950.
[vi] Soares S, Rocha V, Kelly-Irving M, Stringhini S, Fraga S. (2021). Adverse Childhood Events and health biomarkers: A systematic review. Front Public Health. Aug 19;9:649825. doi: 10.3389/fpubh.2021.649825. PMID: 34490175
[vii] Greten FR, Grivennikov SI. (2019). Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. Jul 16;51(1):27-41. doi: 10.1016/j.immuni.2019.06.025. PMID: 31315034