For the first time scientists provided evidence on the effect genetic makeup has on developing cancer, underscoring the need to take personalised care into account.
Many smokers never develop lung cancer, while some lifelong non-smokers do. Likewise, not everyone exposed to sunlight develops skin cancer.
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A new study published in Nature could help explain a longstanding mystery in cancer biology: why people exposed to similar environmental risks often experience dramatically different outcomes.
“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,” Cancer Research UK research information lead, Sam Godfrey, said in a press release.
The researchers found that even relatively modest inherited genetic variation can alter how tumours evolve after exposure to the same cancer-causing DNA damage. They argue that the findings highlight the need to factor inherited genetics and population diversity into future cancer prevention and screening strategies.
The findings suggest that a person's inherited genetic background helps determine which mutations take hold, how tumours develop and potentially how they respond to treatment.
"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,” said Duncan Odom, who led the research while at the CRUK Cambridge Institute and is now based at German Cancer Research Centre (DKFZ) in Heidelberg, Germany.
Researchers used four genetically distinct strains of mice to reflect levels of diveristy similar to those found in humans.
They then exposed them to identical doses of a known liver carcinogen — diethylnitrosamine — which is found in tobacco smoke and some processed foods and is known to cause DNA damage in liver cells, leading to mutations that can initiate tumour growth.
Despite receiving the same dose of carcinogen at the same age – 15 days – under controlled conditions, the animals developed cancers through different evolutionary routes depending on their genetic background. Nearly 600 tumours were analysed to reconstruct how the cancers evolved.
Although many tumours ultimately activated the same biological processes that promote cancer growth, they reached that destination through different mutations and genetic changes, suggesting inherited DNA influences not only cancer risk but also the way the tumour evolves once it begins to form.
Underscoring personalised care need
The researchers say the findings have implications for cancer screening and precision medicine.
“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 author of the study, Sarah Aitken, Assistant Professor at Yale School of Medicine, who also worked on the research at the CRUK Cambridge Institute
The researchers also suggest inherited genetics could influence responses to treatments against tumour DNA, including some forms of chemotherapy and radiotherapy. “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,” Aitken said.
If confirmed in people, that could open the door to more tailored approaches to treatment selection and risk assessment.
“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, and lead to more powerful and precise ways of tackling cancer.” Cancer Research UK research information lead, Sam Godfrey, said.
