Cancer often seems to appear out of the blue. Now the first study of its type shows the patterns of the other diseases people get before developing cancer. Cardiovascular diseases, obesity and genitourinary diseases are most common. The results can be used to better identify and screen the people with the highest risk and to search for new causes of cancer related to genes and lifestyles.
Global populations are ageing. Only a century ago, many people died young from infectious diseases, but as populations age, the disease pathways become more complicated, since many older people have several diseases at the same time. One disease that is increasing rapidly is cancer. To better predict who will develop cancer, Danish researchers analysed historical data from 6.9 million people to determine which diseases people get before developing cancer.
“For all types of cancer as a whole, people most frequently develop cardiovascular diseases, overweight and genitourinary diseases before developing cancer. Given this knowledge, we hope to become better at finding people at high risk of developing cancer and to find genetic links between the diseases to enable us to become better at preventing and detecting cancer early,” explains Søren Brunak, Group Leader, Disease Systems Biology programme, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.
Conclusions are premature
The study is the largest of its type in the world and has only been possible because of the Danish Cancer Registry, which contains data as far back as 1943. The study included data from 700,000 people with cancer. The researchers compared data from the Danish Cancer Registry and the Danish National Patient Registry – a national registry of the activity of all Danish hospitals – and found trends in the disease pathways.
“We had enough data to investigate 17 types of cancer and found clear disease patterns for seven of them. We already knew some of these patterns: for example, people tend to develop chronic obstructive pulmonary disease before they get lung cancer, but some disease pathways have been less prominent, such as many people developing such circulatory diseases as coronary artery spasms and ischaemic heart disease before developing cancer. This is important information that can potentially help doctors to focus early on the potential for these people to develop cancer.”
Thus, the researchers found clear patterns in the diseases developing 10 years before people develop cancer of the breast, prostate, ovaries, lungs, skin and stomach and non-Hodgkin lymphoma, but even though the patterns are quite clear, the researchers emphasize caution in interpreting the patterns of earlier disease as being causally linked to developing cancer later.
“Although the disease pathways are rather obviously and notably associated with developing cancer, we cannot conclude that they are causally related. Just as we know that human papillomavirus (HPV) can lead to cervical cancer, we need to determine whether these diseases cause cancer, so the new results mainly give us ideas about where to look for associations.”
Seeking the Achilles’ heel of cancer
Inflammation is a factor the researchers generally speculate about in relating the early disease pathways to developing cancer later. Cardiovascular diseases, obesity and genitourinary diseases are associated with considerable and long-lasting inflammation if they are not treated.
“Inflammation is a possible and very relevant common denominator, so this is one question we will seek to answer in the years to come. We know that people have far fewer genes than previously thought: about 20,000. This probably means that the same genes can be associated with several diseases, so we are investigating these links.”
In searching for genetic associations, the researchers are also focusing on non-oncogene addiction genes. Previously, cancer research has focused on oncogenes – genes that have the potential to cause cancer – but cancer researchers are increasingly seeking the genes that cancer cells need to survive.
“In our search for links between disease pathways and cancer, we especially focus on finding these genes, because they can prove to be the Achilles’ heel of cancer, which could perhaps be targeted using medicine. While we clarify these links, the results should also be used to focus on the people with these characteristic disease pathways to target those who should be screened regularly.”
“A large-cohort, longitudinal study determines pre-cancer disease routes across different cancer types” has been published in Cancer Research. Jessica Hu is the first author. The study was a collaboration between researchers from the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen and the Department of Infectious Diseases, Rigshospitalet, Copenhagen. In 2017, the Novo Nordisk Foundation awarded the Hagedorn Prize to Jens D. Lundgren, a main author.