It’s Not Your Fault: Cancer as a Multifactorial Disease

It Is Not Your Fault

Cancer has been around forever. One of the biggest reasons we see cancer in our aged dogs is that they can and do get older. We have become much better dog parents, feed healthy well-balanced diets, vaccinate for infectious disease, participate in regular vet visits, minimize wandering, and so on. Because of this our dogs reach the age that they either succumb to organ dysfunction/disease or cancer.¹ Similar things have happened to us humans as we also live longer. As a multifactorial disease, cancer doesn’t have “just one cause” and no one is at fault if it happens.

Multifactorial Disease = There Is No One Cause

Cancer is a multifactorial disease. Simply defined, cancer is the growth of abnormal cells that become malignant and often spread (metastasize) to other parts of the body. Everyone makes mistakes, even cells. Cancer begins as a mutation in cellular DNA. Most of the time, the body removes or corrects the mutation. Sometimes, however, the change persists. When there are too many mutations the cells start to grow into a tumor.

There are numerous risk factors involved, including:²

• Environmental chemicals
• Radiation
• Dietary excess/deficiencies
• Infectious
• Genetics

Additionally, cancer does not develop from a single insult to a cell, but from multiple changes that occur before the cell even becomes a cancer. This happens over time, which is why older dogs are more likely to have cancer.³

Epigenetics

Cells do not read all parts of DNA. Epigenetic factors can change which parts of the DNA a cell reads and which it ignores.

What are epigenetic factors? There are many, but you could think of them as “environmental” factors. Smoking (or secondhand smoke), obesity, lack of sleep, diet, exercise, environmental pollutants, and psychological stress are all examples of epigenetic factors that might affect the way a cell reads its DNA code.

Epigenetic factors (together called the epigenome) don’t change the DNA itself. But epigenetics can change what is ultimately translated from the DNA into the cell’s activities.

Epigenetic factors at the cellular level include:⁴

• DNA methylation
• histone modification
• nucleosome remodeling
• non-coding RNA.

Epigenetic abnormalities in cells are potentially reversible but can mistakenly turn on pathways that alter gene function and can result in cancer.⁵

Immune System

Cancer cells evade the immune system through a variety of complex interactions including restricting antigen recognition (immune cells cannot recognize cancer cells as abnormal), inhibiting immune system including cytokines (signaling proteins), causing T cell exhaustion, and limiting nutrients to the immune system cells creating a tumor microenvironment.⁶ Additionally, pro-inflammatory mediators are known to contribute to tumor development. This is one reason obesity is considered a risk factor for cancer. Fat cells secrete many cellular mediators that contribute to a low-level state of inflammation in the body.⁷

Tumor Microenvironment (TME)

Tumor microenvironment is the environment surrounding the cancerous cells, designed to promote fast cell growth, to spread through the blood or lymphatics, and to suppress the immune system so the tumor can avoid death.⁸ Additionally, cancer cells need a lot of nutrition for growth. Tumor associated macrophages are abundant in the TME, providing nutrients to the cancer cells while also depleting nutrition for the immune cells.^6,9

The Unknown

Ultimately, not every mutation leads to cancer. It is the accumulation of mutations that causes a tumor to form. Additionally, specific mutations are often associated with specific-organ cancers.²

There are also cancer factors that are yet to be discovered. Genetics, epigenetics, and the immune system are all complex multifactorial processes in their own right but they interplay with each other adding another layer of complexity. Hopefully with time and research we will understand more about how cancer forms so that further prevention can happen in the future.

You Did Not Cause Your Dog’s Cancer

Remember, multiple factors contribute to cancer. There is not a single thing that we as owners do that will result in cancer in our dogs. Unfortunately, as we have become caretakers, our dogs are living long enough to develop cancer. The same thing happens to us as humans. Fortunately, doctors are getting better at diagnosing and new treatments are being developed all the time, to help us manage this disease process.