In the past decades, cancer research has made great strides which have translated in tangible advances for patients, such as the advent of personalized medicine. Since we know so much about this disease, you would think the root causes would also be known. In actual fact, this complex topic is still very much a matter of debate.
Cancer is a lengthy and multifactorial pathologic process initiated by genetic mutations that turn normal cells into cancerous cells. If we want to know how cancer starts, we need to understand what causes these mutations.
Heredity plays a role
While some gene mutations are inherited, most of them do not directly cause cancer; rather, they are predisposing factors. This means that the people with these mutations have an increased chance of developing certain types of cancer. Current research indicates that 5% to 10% of cancers have a genetic component. The best known example is carriers of the BRCA1/2 mutation, who have a 65% chance of developing breast cancer before the age of 70.1
Mutations: random or caused by the environment?
Other cancer-causing mutations appear throughout a person’s life and are therefore acquired. These mutations are caused by either external or internal factors. The former, also known as carcinogens (tobacco, asbestos or UV rays, for example), exist in the cell’s microenvironment and introduce mutations. Internal factors are associated with normal cell function. Every time cells divide they need to make a perfect copy of all of their chromosomes, collectively called the genome. However, sometimes “bad luck” causes certain genes to mutate. The scientific community is still divided over the question of whether cancer is caused more by genetic or environmental mutations.
In some cases, the culprit is clear: tobacco has long been known to precipitate the cell mutations that cause lung cancer. However, for many other types of tumors, the question remains unresolved. In 2015, an important study apparently established that most cancer mutations are due to random chance.2 Scientists have proven that the more cells divide, the greater the risk the disease will appear. This explains why, for instance, cancer of the colon (where cell division is frequent) occurs ten times more frequently than that of the esophagus, where cells divide slowly. However, the scientific community is far from unanimous on this issue, and further research suggests that random chance might only account for 10% to 30% of cancer mutations.3
Although the causes of mutations are still being heavily debated, the public health message remains the same: since cancer is caused by several mutations, people should do their best to avoid exposure to carcinogens, thereby reducing the likelihood of mutations based on environmental factors.
Simon Mathien, PhD
Simon holds a doctorate in molecular biology from the University of Montreal. He works hard to understand the cellular mechanisms of cancer and is passionate about popularizing scientific knowledge, so he can tell the general public and advances in biomedical research.
1 : Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics 2003; 72(5):1117–1130.
2 : Tomasetti, C., and Vogelstein, B. (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347, 78-81.
3 : Wu, S., Powers, S., Zhu, W., and Hannun, Y.A. (2016). Substantial contribution of extrinsic risk factors to cancer development. Nature 529, 43-47.