Why do some lifelong smokers never develop lung cancer while others who have never smoked are diagnosed with the disease? A new study suggests that part of the answer may lie in a person's inherited genetic makeup.
Researchers have uncovered the first direct evidence showing that an individual's genes can influence how DNA responds to environmental exposures such as cigarette smoke and sunlight, ultimately affecting the number of mutations that accumulate over time. The findings, published in the journal Nature, could reshape scientists' understanding of cancer risk and improve future screening and prevention strategies.
Study links inherited genes to DNA damage
The international research team, including scientists from the University of Cambridge, found that inherited genetic differences can alter the way DNA is damaged by environmental carcinogens and how those damaged cells evolve into cancer.
Previous research had suggested that genetics influences cancer risk, but proving the connection has been difficult because people's lifestyles, environments and exposure to harmful substances vary significantly.
By using genetically diverse laboratory mice raised under identical conditions, researchers were able to isolate the role of inherited genetics from environmental factors for the first time.
Why don't all smokers develop cancer?
The findings may help explain one of cancer research's biggest questions: why many smokers never develop lung cancer, while some people who have never smoked are diagnosed with the disease.
As quoted by PTI, senior author Duncan Odom, who led the research while at the Cancer Research UK Cambridge Institute at the University of Cambridge, said, "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."
He added that the study demonstrates, for the first time, how inherited genetic background influences both the mutation process and the biological pathways that eventually lead to tumour development.
How researchers conducted the study
To understand the role of genetics, researchers bred four strains of mice with varying levels of susceptibility to liver cancer.
The mice were then exposed to an identical dose of diethylnitrosamine (DEN), a chemical carcinogen found in tobacco smoke and certain processed foods that is known to damage DNA in liver cells.
Because every mouse received the same dose at the same age under carefully controlled laboratory conditions, researchers were able to eliminate environmental differences that often complicate human studies.
The team subsequently sequenced the genomes of nearly 600 tumours, analysed gene activity and compared tumour development with untreated mice to reconstruct how each cancer evolved from its earliest mutation.
Researchers found common cancer pathways but different genetic responses
Although tumours across all mouse strains activated the same cancer-driving signalling network, known as the MAPK pathway, inherited genetics influenced how cancers continued to evolve afterwards.
Researchers found that different genetic backgrounds altered the activity of additional cancer-related pathways and affected the likelihood of whole-genome duplication, a process in which cells acquire an extra copy of their entire genome. This can create additional gene copies that may later accumulate mutations and contribute to tumour growth.
What do the findings mean for cancer screening?
The researchers believe the findings could have important implications for cancer prevention, early detection and precision medicine.
Rather than relying solely on environmental risk factors such as smoking or sunlight exposure, future screening programmes may also need to consider inherited genetic differences when assessing an individual's cancer risk.
As reported by PTI, the team said prevention strategies and personalised treatments could become more effective by accounting for both genetic background and population diversity.
Why the study matters
The research provides some of the strongest evidence to date that cancer risk is shaped by a combination of environmental exposures and inherited genetics.
While lifestyle choices such as avoiding tobacco, limiting excessive sun exposure and maintaining a healthy lifestyle remain among the most effective ways to reduce cancer risk, the study suggests that a person's genetic inheritance also plays a significant role in determining how the body responds to DNA damage.
The findings offer fresh insights into why cancer develops differently from one individual to another and may help pave the way for more personalised approaches to prevention, screening and treatment.
Disclaimer: This article is intended for informational purposes only and should not be considered a substitute for professional medical advice, diagnosis or treatment. Always consult a qualified healthcare professional or your doctor if you have any questions or concerns about a medical condition. Never disregard or delay seeking medical advice based on information you have read here.
