Why Some Smokers Never Get Cancer

Although smoking is linked to cancer risk, some smokers never develop cancer in their lifetime. On the other hand, some people who have never smoked end up with cancer. What is the cause?

A new study published in the journal Nature offers clues about the reasons behind differences in how the body responds to cancer-causing exposures. The research shows that a person’s genetic factors can play a major role in determining how cancer develops after DNA damage occurs.

“This study gives us a fascinating clue that the genes we inherit may have a major influence on the way cancer develops after DNA damage,” said Sam Godfrey, head of research information at Cancer Research UK, quoted by Euronews on Tuesday (28/7).

The researchers found that inherited genetic variations, even at relatively small levels, can affect how tumours evolve after DNA damage caused by the same carcinogen. Genetic factors also play a role in determining which mutations develop, how tumours form, and how the cancer is likely to respond to treatment.

Duncan Odom, who led the study while still working at the CRUK Cambridge Institute, said the research shows for the first time the extent to which genetic background influences the mutation process and the pathways leading to tumour development. “We managed to show for the first time the extent to which genetic background influences the mutation process and the pathways that lead to tumour development,” said Odom.

In the study, the scientists used four strains of mice with genetic differences to represent a level of genetic diversity similar to that found in humans. All the mice were exposed to the carcinogen that causes liver cancer, diethylnitrosamine (DEN).

The DEN compound is known to be present in tobacco smoke and some processed foods. DEN can cause DNA damage in liver cells, which then triggers mutations that can mark the beginning of tumour formation.

The exposure was carried out under highly controlled conditions. All the mice received the same dose of the carcinogen at the same age, namely when they were 15 days old.

However, despite identical exposure, cancer development in the mice proceeded along different evolutionary pathways, depending on their respective genetic backgrounds. The researchers analysed nearly 600 tumours to reconstruct how the cancer developed and changed over time.

The results showed that many tumours ultimately activated the same biological processes that drive cancer growth. However, the tumours reached that state through different mutations and genetic changes.

These findings demonstrate that cancer is influenced not only by external factors, such as exposure to carcinogens, but also by a person’s inherited genetic makeup, which determines the evolutionary pathway of the cancer once a tumour begins to form.