Many early-onset colon cancers are caused by genetic mutations passed through families

December 15, 2016
A new study published by The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute found that one in every 16 colorectal cancer patients diagnosed under age 50 had an inherited genetic mutation that made them more susceptible to developing cancer. Credit: The Ohio State University Comprehensive Cancer Center

One in every six colorectal cancer patients (16 percent) diagnosed under age 50 has at least one inherited genetic mutation that increases his or her cancer risk and many of these mutations could go undetected with the current screening approach, according to initial data from a statewide colorectal cancer screening study conducted at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

In this new analysis, the OSUCCC - James team offers the first detailed report of the prevalence and spectrum of specific mutations in 25 genes associated with inherited (passed down through families) cancer syndromes in an unselected series of colorectal cancer patients. The study includes data from 450 patients with early-onset colorectal cancer recruited from a network of hospitals throughout the state of Ohio.

"The prevalence of hereditary cancer syndromes among early-onset colorectal cancer patients - including Lynch syndrome - was quite high, which presents a tremendous opportunity for us to save lives through early detection based on genomic risk factors," says Heather Hampel, MS, CGC, principal investigator of the statewide study and senior author of the paper. "It is critical that people find out at a young age if they are genetically predisposed to cancer so they can take steps to prevent cancer from occurring at all."

Multi-gene testing uses next-generation sequencing to screen multiple cancer genes simultaneously with one blood sample. Previous studies have shown that multi-gene panel testing for hereditary colorectal cancer is feasible, timely and more cost-effective than single gene testing, but the utility of such testing in this patient population was previously unknown.

The video will load shortly.
Credit: The Ohio State University Comprehensive Cancer Center

Based on this new data, the OSUCCC - James research team recommends genetic counseling and a broad, multi-gene panel test of cancer susceptibility genes for all early-onset colorectal cancer patients, regardless of family history or the results of tumor screening for Lynch syndrome. This differs from current professional guidelines, which recommend all colorectal cancer patients be screened for Lynch syndrome, with referral for genetic counseling and Lynch syndrome-specific genetic testing if the tumor-screening test is abnormal.

The team's findings, however, showed that 33 percent of patients found to have an inherited cancer syndrome did not meet established testing criteria for the gene in which they were found to have a mutation.

"We expected to find a high rate of Lynch syndrome among these early-onset colon cancer patients. What was surprising were some of the other gene mutations found in the young colorectal cancer patients, including mutations in genes traditionally linked to breast cancer risk, even in patients whose family history was not suggestive of those mutations," said Rachel Pearlman, MS, CGC, first author of the paper and statewide study coordinator. "Until multi-gene panel testing, we typically would not have tested a patient with colorectal cancer for mutations in those genes unless they met criteria based on their family history. There is still a lot to learn from these findings."

They report their findings in the Dec. 15, 2016, issue of the medical journal JAMA Oncology.

Nancy Rosen and her son, Michael Greene, have Lynch syndrome, an inherited genetic mutation that puts them at a very high lifetime risk for cancer, most commonly colorectal cancer. Credit: The Ohio State University Comprehensive Cancer Center

Study Design and Results

For this study, researchers recruited 450 patients who had undergone surgery for newly diagnosed, invasive colorectal cancer on or after Jan. 1, 2013. All were between the ages of 17 and 49 and enrolled in the Ohio Colorectal Cancer Prevention Initiative (OCCPI), a statewide colon cancer screening and prevention study aimed at screening all newly diagnosed colorectal cancer patients in Ohio for Lynch syndrome and other hereditary cancer syndromes. Led by Hampel, the OCCPI includes 51 hospital partners across the state of Ohio.

Blood and tumor samples were collected from each patient and tumor pathology characteristics were verified prior to testing. All tumors were screened for microsatellite instability and/or abnormal immunohistochemistry, characteristics that are found in cancers from individuals with Lynch syndrome. All colorectal cancer patients diagnosed under age 50 underwent genetic testing for 25 cancer susceptibility genes [including the genes that cause Lynch syndrome (MLH1, MSH2, EPCAM, PMS2 and MSH6)] using a multi-gene panel.

Overall, 75 cancer susceptibility gene mutations were identified in 72 patients. Eight percent (36 patients) had Lynch syndrome only, 0.4 percent (2 patients) had Lynch syndrome plus another hereditary cancer syndrome, 7.6 percent (34 patients) had a different hereditary cancer syndrome (including a third patient with two syndromes).

"Our study shows that the spectrum of mutations in early-onset colorectal cancer is much broader than we originally thought—both in the number of different gene mutations causing this disease and rates at which they occur," adds Hampel. "We believe this data offers additional support for complete genetic testing for all early-onset colorectal patients. This could save lives by identifying at-risk families so that they can benefit from intensive cancer surveillance and prevention options."

Explore further: Germline TP53 mutations in patients with early-onset colorectal cancer

More information: JAMA Oncol. Published online December 15, 2016. DOI: 10.1001/jamaoncol.2016.5194

Related Stories

Germline TP53 mutations in patients with early-onset colorectal cancer

March 12, 2015
In a group of patients diagnosed with colorectal cancer at 40 or younger, 1.3 percent of the patients carried germline TP53 gene mutations, although none of the patients met the clinical criteria for an inherited cancer syndrome ...

Prostate cancer tied to higher colorectal cancer risk

March 1, 2016
(HealthDay)—The risk of colorectal cancer is increased after a diagnosis of prostate cancer, according to a study published online Feb. 25 in Cancer.

One in seven colorectal cancer patients diagnosed before recommended screening age

January 25, 2016
Nearly 15 percent of patients diagnosed with colorectal cancer were younger than 50, the age at which screening recommendations begin.

New cancer type with PIK3CA mutations

August 16, 2016
A newly defined type of colorectal and endometrial cancer involves at least two somatic mutations in the mismatch repair genes (MMR): MLH1, MSH2, MSH6, PMS2. This double somatic MMR cancer has no germline mutations in the ...

AGA recommends all patients with colorectal cancer get tested for Lynch syndrome

September 10, 2015
All colorectal cancer patients should undergo tumor testing to see if they carry Lynch syndrome, the most common inherited cause of colorectal cancer, according to a new guideline published in Gastroenterology, the official ...

Most cancer patients believe surgery will be curative

October 8, 2015
(HealthDay)—Most patients undergoing surgery for lung or colorectal cancer believe that the surgery is likely to be curative, according to a study published in the Oct. 15 issue of Cancer.

Recommended for you

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.