Research from Icahn School of Medicine at Mount Sinai shows that age of cancer onset is a strong differentiator between individuals in terms of molecular features.
The research team found that immune response to cancer tended to differ in people aged 50 or younger compared to older individuals and that there were also differences in treatment response to various targeted medications, suggesting age should be taken into account when considering treatment options.
“In the US and multiple countries, cancer incidence and mortality have steadily declined in adults over the age of 50,” wrote lead author Kuan-lin Huang, an assistant professor at the Icahn School of Medicine at Mount Sinai, New York, and colleagues in the journal Cell Reports.
“Alarmingly, the overall decline is coupled with a recent rise in the incidence of various cancer types among young adults, including colorectal, endometrial, gallbladder, multiple myeloma, pancreatic, and renal cancer, for individuals between 15 and 50 years old in the US and worldwide.”
For this reason, and because many cancer studies are based on results from older individuals, Huang and team assessed genomic profiles of individuals with the same types of cancer but differing ages of onset to see how they differed. Overall, they included 6000 cases, 1757 aged 50 years or younger at onset and 3608 who were older than 50, in their study across 14 cancer types.
The results showed some interesting variation between the age groups. Tumors in younger individuals generally had a lower mutation burden and a similar copy number variation rate to those in older individuals. However, “they are enriched for multiple driver mutations and copy-number alterations in subtype-specific contexts,” write the authors.
A closer look at the tumor microenvironments showed that tumors from the younger group tended to have a higher dendrite-led TGF-beta response and a lower macrophage-led IFN-gamma response than tumors from older individuals.
As well as overall differences, the researchers found there were also age-related differences within specific cancer types. For example, the most common type of genetic mutations seen in young adult gliomas differed from those seen in older patients. In endometrial cancer, younger patients had significantly more mutations in their tumors than older patients.
The research team also looked at how these differences could impact treatment. They found answers as to why some targeted treatments work better in different age groups. For example, their results suggest that drugs targeting BRAF gene mutations might be more effective in younger skin cancer patients than in older individuals.
“Our comprehensive assessment revealed the molecular etiologies of young adult tumors across multiple cancer types. The findings highlighted key genomic and microenvironment alterations that may be targeted by kinase inhibitors and immunotherapies, presenting possible treatment options for young adult cancer patients,” concluded the authors.