Research finds colorectal cancers of young adults have changes in the genes FBXW7 and POLE

Summary

This research compared specific genes in colorectal tumors of younger adults to older adults.

  • Younger adults were age 45 or younger when diagnosed with colorectal cancer
  • Older adults were age 65 or older when diagnosed with colorectal cancer

What were the main results?

Researchers found mutations (changes) happened more often in 2 genes in the tumors of young adults than in older adults.

These genes were:

  • FBXW7 – previous research had linked changes in this gene with worse survival in colorectal cancer
  • POLE – previous research had linked changes in this gene to colorectal cancer in young adults with no known family history

Researchers also found that mutations in 4 other genes were similar in younger and older adults or slightly higher in older adults.

Further study of FBXW7 and POLE mutations may help with future screening and treatment for younger adults with colorectal cancer.

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    What did researchers study?

    Researchers looked for any gene mutations in colon and rectal tumor samples that had been frozen between 1998 and 2010. Researchers compared the tumors’ DNA to find differences in gene mutations between tumors from younger and older adults.

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    How many patients' data did researchers study?

    Researchers began with colorectal cancer tumor samples from 283 patients who had joined Total Cancer Care® (TCC). They didn’t include tumors from patients who had a family history of cancer or genetic changes that affect tumor cells’ ability to correct errors in DNA (called MSI-high tumors). In total, they looked at:

    • 51 tumors from patients age 45 or younger
    • 195 tumors from patients age 65 or older
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    What kind of research was this?

    This was an observational study. Researchers looked at (observed) samples from frozen and stored colorectal cancer tumors.

The results of this research alone should not be used to make health decisions. It takes many studies for researchers to confirm findings and use them in patient care.

Why was this research needed?

Colorectal cancer is the second leading cause of death from cancer in the United States. Colorectal cancer mainly occurs later in life. On average, people are 65 years old when they are diagnosed with colorectal cancer. Advances in screening and treatment have helped older adults with colorectal cancer live longer.

However, the number of young adults diagnosed with colorectal cancer is going up, and most do not have a family history of the disease. Younger adults often have worse survival compared to older adults.

Researchers think that genetic differences may explain the difference in survival between younger and older adults with colorectal cancer.

This research looked for and compared gene mutations in colon and rectal tumor samples of younger and older adults.

  • How many patients' data did researchers study?

    Researchers began with colorectal cancer tumors from 283 patients in Total Cancer Care® (TCC). This research included tumors at all 4 cancer stages from both younger and older adults. All of the patients had:

    • Been diagnosed with colon and rectal cancer
    • Their tumor sample frozen and stored between 1998 and 2010

    Researchers didn’t include tumors from patients who had a family history of cancer or genetic changes that affect tumor cells’ ability to correct errors in DNA (called MSI-high tumors). This helped make sure that a patient didn’t already have a higher chance for cancer.

    Their final analysis included 246 tumor samples:

    • 51 tumors from patients age 45 or younger when diagnosed with colorectal cancer
    • 195 tumors from patients age 65 or older when diagnosed with colorectal cancer

  • What kind of research was this?

    This was an observational study. Researchers looked at (observed) samples from frozen and stored colorectal cancer tumors.

    This kind of study can further cancer research aimed at developing new treatments, tailoring treatments to patients, and identifying a patient’s cancer sooner.

  • What happened during this research?

    Researchers removed DNA from tumor samples for sequencing.
    Sequencing is when researchers identify the order of the DNA building blocks in a patient’s genes. It allows them to look for differences in genes and gene mutations.

    In this study, researchers sequenced and looked for any gene mutations between the tumors of younger and older adults. Researchers looked at differences in:

    • Mutations at certain locations on a gene
    • The entire gene for a mutation

    Researchers then compared the gene mutations of the younger and older adults to identify any differences in how often they happened.

  • How researchers designed this study

    Researchers started with tumor samples from 283 patients. Researchers didn’t include 58 patients due to family history of cancer and MSI-high tumors.

    Researchers sequenced DNA from 246 tumor samples.

    • 195 tumors were from patients 65 years or older
    • 51 tumors were from patients 45 years or younger (including 21 tumors added later)

    Researchers compared differences in gene mutations.

    See infographic

  • What were the main results?

    Researchers found mutations (changes) that happened more often in 2 genes in the tumors of younger adults than in older adults:

    • FBXW7 (F-box/WD repeat containing protein 7) – previous research had linked changes in this gene with worse survival in colorectal cancer
    • POLE (polymerase epsilon catalytic subunit) – previous research had linked changes in this gene to colorectal cancer in young adults with no known family history

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    Other results

    Researchers also found mutations in 3 other genes that happened similarly between younger and older adults. These genes are named TP53, KRAS, and APC. Mutations in a gene named BRAF happened slightly more often in older adults.

  • How has this research helped?

    The researchers found gene differences in the colorectal cancers of younger adults compared to older adults. They believe that the higher rates of FBXW7 and POLE gene mutations in the colorectal cancers of younger adults may:

    • Help explain why young adults have worse survival
    • Suggest immunotherapy as a potential treatment for younger adults. Immunotherapy is a type of cancer treatment that uses the body’s own immune system to help detect and fight cancer

    Researchers suggest further study of these mutations to confirm their results. Further study may also help future screening and treatment for younger adults with colorectal cancer.