Why Do We Get Cancer? What We Know, What We Don't Know, and What We Underestimate

Cancer patients cannot help questioning why they have this disease. What were the causes of this disease? Was it something they did or could have prevented?

As oncologists, we think that 40% of all cancers can be explained by known and usually modifiable risk factors; so almost half of them are preventable! Smoking and obesity are the primary precursors, but many other factors (germline mutations, alcohol, infections, and pollutants such as asbestos) increase the risk of developing cancer.

But what do we know about the remaining 60%?

For this remainder, a new study has shown that while cancers are likely to be influenced by underlying lifestyle or environmental factors, experts still don't understand their actual development stories. A small but significant number may be due to (bad) luck.

Here are the things that oncology researchers suspect about the still unknown causes of cancer, and why it's so hard to confirm them.

Possibility 1: Known Risk Factors May Be More Effective Than We Think

Let's start with cigarettes, for example. With decades of research, scientists have clearly defined the carcinogenic effects of tobacco. The researchers found that cells growing in a plaque undergo a unique set of mutations in tumors that develop in smokers when exposed to carcinogens found in tobacco.

In addition, experts are able to gather robust data from epidemiological studies on the prevalence of smoking, as well as associated cancer risks and mortality, as it is relatively easy to measure an individual's lifetime tobacco exposure at large.

"The evidence against smoking is incredibly consistent," says epidemiologist Paul Brennan of the World Health Organization's International Agency for Research on Cancer.

For other known risk factors, such as obesity and air pollution, there are more questions than answers. Professor of Clinical Epidemiology from the University of Bristol, UK. Richard Martin says that because of the limitations on how to measure these factors, we're probably downplaying their effects.

Let's take obesity. Being overweight increases the risk of developing at least 13 cancers. Although risk estimates vary depending on studies and cancer types, being overweight or obese accounts for approximately 4% of all cancers worldwide – 1% in low-income countries and 8% in high-income countries.

However, Brennan thinks we underestimate the impact obesity has on cancer.

He says the main reason for this is that people use the Body Mass Index (BMI) to calculate their excess weight, which is a poor tool that cannot be used for measuring body fat. The BMI does not distinguish between fat and muscle, which means that a person who is the same height and weight as an athlete who eats lean meats and vegetables, but leads a sedentary lifestyle and consumes large amounts of processed food and alcohol, may have the same BMI.

Furthermore, studies looking at BMI only calculate a person's BMI once, and no single measurement will tell you how a person's weight has fluctuated in recent years or at different stages of life. However, recent analyzes suggest that obesity status over time may be more associated with cancer risk than one-time measures. In addition, many studies now suggest that changes in our gut microbiota and our high blood insulin levels – which often happen in people who are obese or overweight – can increase cancer risk and accelerate tumor growth.

Given these additional factors, the effect of excess body fat may ultimately play a much more important role in cancer risk. In fact, according to Brennan, "if we can accurately predict the effects of obesity, we may see it become the main cause of cancer."

Possibility 2: Keeping Lifestyle or Environmental Factors Under the Radar

Researchers have associated many substances that we consume or are exposed to in our daily lives with cancer. But it is largely unknown what potential carcinogens in our environment, especially those nearly ubiquitous, are and to what extent they affect them.

A simple reason for this is that the effects of many of these substances are difficult to assess. For example, while it is possible to compare a person who smokes a pack of cigarettes a day to a non-smoker, it is more difficult to examine the effects of pollutants found in water and food compared to tobacco in a given population.

“If there are ubiquitous risk factors to which we are exposed, it can be difficult to discern their (each individually) role. There are (probably) a lot of causes that we really don't know, and everyone is exposed to them." says.

“People in their 40s may not reflect what they were exposed to on the playground or football field at the age of 5 to 10,” said Graham Colditz, an epidemiologist and Public Health Specialist at the University of Washington. Technology continues to change, so we can better measure what we're exposed to today, but the relevance of that 5, 10, 15 years ago was probably very variable.” says.

The researchers also found that most carcinogens do not directly cause specific mutations in a cell's DNA; on the contrary, they argue that most carcinogens cause cancer-causing changes in cells, such as inflammation.

“We need to think about how potential carcinogens cause cancer. Potential carcinogens, rather than causing mutations, are another kind of pathway entirely.” says. For example, when inflammation becomes chronic, it can promote a series of events that eventually lead to cancer.

Most research to date has been done in high-income countries such as the USA, Australia, and parts of Europe. So we don't know much about what causes cancer in low- and middle-income countries. Addressing this uncertainty, Molecular Epidemiologist Marc Gunter of the International Agency for Research on Cancer states that "there is a lack of strong epidemiological studies in other parts of the world, in Africa, Latin America, and parts of Asia."

Possibility 3: Some Cancers can Occur by Chance

When it comes to cancer risk, (bad) luck can also play a role as an element.

Cancers most often occur in individuals exposed to known carcinogens or with a family history of cancer. However, Gunter said, “We all know that there are people who eat very healthily, have never been overweight and have never smoked, but have had cancer. And on the contrary, there are those who do not get cancer.” says.

How Much of Cancer Can Be Attributed to Chance?

A controversial study published in the journal Science in 2017 suggested that only about one-third of cancers may be due to environmental or genetic factors, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body. For the remainder, the authors of the study argue that it is caused by random mutations accumulating in a person's DNA – in other words, bad luck.

Conclusion

Whether some cancers are caused by bad luck or other undiscovered risk factors remains an unanswered question.

But the real bottom line is that many unknown causes of cancer are most likely related to lifestyle or environmental factors, meaning that in theory they can be changed or even prevented.

“There will always be some (bad) element of luck, but you can turn your luck around depending on your lifestyle and perhaps other factors we don't fully understand yet,” Gunter says.

The good news is that when it comes to prevention, there are many ways we can change our behavior to increase our chances of cancer-free survival – eating less processed meat and food, exercising daily, going for a walk, or getting vaccinated against cancer-causing viruses.

As scientists better understand what causes cancer, the possibilities for action will increase. After all, cancer is a group of diseases whose history is even older than the history of humanity. There is a steady and slow growth (in knowledge) that reduces cancer risk, yet we will never be able to eradicate cancer, but the days may not be far away when we can control it as a disease.