Scientists have finally uncovered why some tobacco smokers are more likely to get cancer at some point in their lifetime compared to others, even when smoking the same amount. Moreover, while it is common knowledge that smoking increases your chances of developing the disease, your genetic makeup also plays a key role in influencing your personal risk of cancer, according to a groundbreaking new study.
Smoking is linked to at least 15 different types of cancer overall, while smokers are 15 to 30 times more likely to be diagnosed with lung cancer compared to non-smokers. However, most smokers do not develop lung cancer, and some non-smokers do develop lung cancer. The reason why has been a long-standing medical mystery, but now we have a genetic answer.
Cambridge Study in Nature Reveals Genetic Background Shapes Cancer
The research conducted by scientists at the University of Cambridge and published in the prestigious journal Nature revealed that ‘inherited genes interacting with acquired genetic mutations shape how tumours evolve’.
Involving mice, experts at the Cancer Research UK (CRUK) Cambridge Institute at the University of Cambridge worked on an experimental approach to demonstrate how a genetic background can alter how cancer can arise and even evolve over time. This is the first time direct experimental proof has been provided.
Four strains of mice were bred to have varying susceptibility to liver cancer, which spanned different genetic makeups comparable to the genetic diversity seen in human populations.The mice were then exposed to a single dose of the liver carcinogen diethylnitrosamine (DEN), which is found in tobacco smoke and some processed foods and is known to cause direct damage to DNA in liver cells that can ultimately lead to cancer.
Experts were able to eliminate environmental factors as all four strains of mice were bred and exposed at 15 days of age under completely controlled conditions with the same dose. Therefore, any difference in cancer development had to be due to genetics alone.
How Inherited Genes Decide If Cancer Develops
The genomes of almost 600 tumors were then sequenced and studied by the health experts. They discovered that cancers, for the most part, acquired a cancer-driving mutation that activated the same cancer-promoting signalling system in all mice.
To put this in more simple terms, this system, called the MAPK pathway, controls cell growth and cell differentiation, while it is also important in a number of cancer variants. It is a multi-step cascade of molecular signals that tells cells when to grow.
However, the inherited genetics of the mouse played a crucial role in deciding the path. Depending on the genetic background, the particular driver mutation acquired altered the activity of other cancer-associated signalling pathways, as well as causing a striking tendency for whole-genome duplication, an event in which the entire set of chromosomes is doubled, making cancer more aggressive.
“Cancer does not arise entirely by chance. Although tumours often reach the same biological endpoint, the path to that endpoint is determined by an individual’s genetic background,” said senior author Professor Duncan Odom, who led the research while at CRUK Cambridge Institute and is now based at DKFZ in Germany.
“We’ve been able to show for the first time the extent to which genetic background influences both the mutation processes and the pathways leading to tumour development,” he added.
What This Means for Future Cancer Screening and Treatment
The researchers say the findings have profound implications for cancer screening and precision medicine in humans. Tumours arise when our DNA accumulates errors, or mutations, causing cells to grow faster and ignore signals that would otherwise instruct damaged cells to die. Environmental exposures like cigarette smoke influence how much damage occurs, but inherited genetics alters how many mutations accumulate and how the tumour evolves.
“If genetic background influences both cancer risk and the evolutionary trajectory of tumours, future cancer prevention and screening strategies will need to take into account inherited genetics and population diversity,” said first author Dr Sarah Aitken, Assistant Professor at Yale School of Medicine.
“Similarly, how people respond to cancer drugs is likely to differ depending on their inherited genetics, and so we may need to tailor our diagnostics and treatments accordingly,” she added.
Cancer Research UK research information lead, Dr Sam Godfrey, said: “This study gives us a fascinating hint that our inherited genes might have a big influence on the way that cancers develop after DNA damage. We still need to see more research before we can understand what this means in humans, but this finding could change our understanding of how cancer starts.”
Final Analysis: Genes Load the Gun, Smoking Pulls the Trigger
This landmark Nature study solves a key puzzle: why some heavy smokers never get cancer while some light smokers do. Smoking provides the DNA damage through carcinogens like DEN, but your inherited genes decide how your body handles that damage, which mutation pathway is taken, and whether a tumour becomes aggressive. Therefore, there is no safe level of smoking, as you cannot know your genetic vulnerability.
FAQ
1. Why do some smokers get cancer and others don’t?
According to the Cambridge study in Nature, inherited genetic background interacts with DNA damage from tobacco. Genes determine mutation processes and pathways leading to tumour development, so same smoking exposure leads to different cancer risk in different people.
2. What is DEN found in tobacco?
DEN or diethylnitrosamine is a liver carcinogen found in tobacco smoke and some processed foods that causes DNA damage in liver cells, leading to mutations that can initiate tumour growth, used in the mice study to control exposure.
3. How many cancers are linked to smoking?
Smoking is linked to at least 15 different types of cancer overall, and smokers are 15 to 30 times more likely to be diagnosed with lung cancer compared to non-smokers, as per global cancer data.
4. What is MAPK pathway in cancer?
MAPK pathway is a multi-step cascade of molecular signals controlling cell growth and differentiation. The study found cancers across all genetic backgrounds nearly always acquired a mutation activating this same cancer-promoting system, but genetic background altered other pathways.
Disclaimer: This article is for general informational and educational purposes only and is based on research published in Nature by the University of Cambridge and Cancer Research UK. It does not constitute medical advice, diagnosis, or treatment. The study was conducted in mice under controlled conditions and findings in humans are still being researched. Smoking is a proven major risk factor for at least 15 types of cancer and many other diseases, regardless of genetic background. There is no safe level of tobacco use. If you smoke and want to quit, or have concerns about cancer risk or family history, please consult a qualified healthcare professional, oncologist, or de-addiction specialist. Our news portal and its authors assume no liability for actions taken based on this information.
