Lynch syndrome found to be associated with more types of cancers

June 4, 2018 by Bob Yirka, Medical Xpress report
Micrograph showing tumour-infiltrating lymphocytes in colorectal carcinoma. H&E stain. Credit: Nephron/Wikipedia/CC BY-SA 3.0

A team of researchers at Memorial Sloan Kettering Cancer Center has found Lynch syndrome to be associated with more types of cancer than previously thought. The group gave a presentation at this year's American Society of Clinical Oncology meeting outlining their findings.

Lynch syndrome is an inherited condition that results in a higher risk of developing certain types of cancer. Up until now, the elevated risk was thought to be restricted mostly to colon and endometrial cancers. But in this new effort, the researchers found evidence that suggests it can also be associated with other types of cancer, such as prostate, melanoma, ovarian germ cell, sarcoma and mesothelioma—and possibly many others.

Patients who develop endometrial or are typically screened for Lynch syndrome, because if markers for it are present, they are likely to be more susceptible to developing it as well. Those who have been identified with it, including the initial patient, can then be offered options to reduce their risk factors or even to treat their tumors—the FDA has an approved therapy list for patients with Lynch syndrome.

The team was conducting a genetic study of tumor samples. They looked at 15,000 samples that included 50 different types of cancer. In particular, they were looking at those with high microsatellite instability (MSI-H) which not only increases the odds of a tumor spreading but of the patient having Lynch syndrome. As part of their analysis, the researchers found that approximately 16 percent of those patients with tumors who had high MSI-H also had Lynch Syndrome. Furthermore, they also found that approximately half of all the tumors they tested that came from patients with Lynch syndrome were not due to colon or . This, the researchers noted, suggests that many more need to be screened for Lynch syndrome than previously.

The researchers conclude that screening for Lynch syndrome accompanying other types of cancers can be done immediately. Doctors need not wait for further results. Patients and their families can start benefiting right away.

Explore further: Two new breast cancer genes emerge from Lynch syndrome gene study

More information: Pan-cancer microsatellite instability to predict for presence of Lynch syndrome,


Background: The success of immunotherapy in microsatellite unstable (MSI-H) and/or DNA mismatch repair deficient (MMR-D) tumors has resulted in routine MSI-H/MMR-D testing in advanced solid tumors. Unlike colorectal (CRC) and endometrial cancer (EC), where this has long been undertaken, the characterization of Lynch syndrome (LS) across heterogeneous MSI-H/MMR-D tumors is unknown. Methods: Through a targeted NGS panel, MSI status was determined via MSIsensor. Scores of < 3, ≥3 to < 10, or ≥10 designated Microsatellite stable (MSS), MSI-Indeterminate (MSI-I) or MSI-H status, respectively. Germline mutations were assessed in MLH1, MSH2, MSH6, PMS2, EPCAM. Immunohistochemical staining (IHC) for MMR-D and tumor signatures in LS patients were assessed. Clinical variables were correlated with MSI and compared via Chi square or T-test. Results: Of 15,045 tumors spanning > 50 cancers , 93.2% were MSS, 4.6% MSI-I, and 2.2% MSI-H. Germline mutations were identified in 0.3% (37/14,020), 1.9% (13/699), and 16.3% (53/326) in the MSS, MSI-I, and MSI-H groups, respectively (p-value < 0.001). 25% of 1,025 MSI-H/MSI-I tumors were CRC/EC, but 50% (33/66) of LS patients had MSI-H/MSI-I tumors less commonly or not previously associated with LS (mesothelioma, sarcoma, adrenocortical, melanoma, ovarian germ cell). LS pts with MSI-H/MSI-I non-CRC/EC tumors only met testing criteria in 63.6% of cases, had lower MSIsensor scores, and were more likely to be MSI-I (MSI-I: non-CRC/EC, 30.3% (10/33) vs CRC/EC 9.1% (3/33); p-value = 0.03). IHC was completed in 86.4% (57/66) of LS MSI-H/MSI-I tumors, with 98.3% MMR-D-concordance. Of LS pts with MSS tumors, 78% had MSH6/PMS2 mutations, but 71% of LS pts with MSI-H/MSI-I tumors had MLH1/MSH2/EPCAM mutations(p-value < 0.001). 89% (33/37) of MSS tumors of LS pts had non-MMR-D signatures. Conclusions: MSI-H/MMR-D is predictive of LS across tumor types and suggests a more heterogeneous spectrum of LS-associated cancers than previously appreciated. Nearly 40% of LS pts with MSI-H/MMR-D non-CRC/EC tumors did not meet clinical criteria for genetic testing, suggesting that MSI-H/MMR-D tumors, regardless of cancer type or family history, should prompt germline testing for the evaluation of LS.

Related Stories

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

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 ...

Evidence mounts for endometrial cancer tumor testing to identify women with Lynch syndrome

December 11, 2013
A recent article by Norris Cotton Cancer Center researchers published in the January 2014 issue of the journal Clinical Chemistry reviews the scientific evidence that warrants screening all endometrial cancers for Lynch syndrome. ...

Prostate cancer risk rises in men with inherited genetic condition

April 1, 2013
Men with an inherited genetic condition called Lynch syndrome face a higher lifetime risk of developing prostate cancer and appear to develop the disease at an earlier age, according to a new study led by researchers at the ...

Mesalazine attenuates tumour formation by 50% in hereditary bowel cancer cases

May 14, 2018
Around 5,000 Austrians a year develop a colorectal carcinoma, that is to say cancer of the colon or rectum. Around 5% of these are genetically predisposed and develop Lynch syndrome, the commonest genetic form of bowel cancer, ...

Snack attack: Eating unhealthy snack foods may affect cancer risk in patients with Lynch syndrome

December 17, 2012
A new analysis has found that loading up on snack foods may increase cancer risk in individuals with an inborn susceptibility to colorectal and other cancers. Published early online in CANCER, a peer-reviewed journal of the ...

Recommended for you

Scientists discover new method of diagnosing cancer with malaria protein

August 17, 2018
In a spectacular new study, researchers from the University of Copenhagen have discovered a method of diagnosing a broad range of cancers at their early stages by utilising a particular malaria protein that sticks to cancer ...

Pregnant? Eating broccoli sprouts may reduce child's chances of breast cancer later in life

August 16, 2018
Researchers at the University of Alabama at Birmingham have found that a plant-based diet is more effective in preventing breast cancer later in life for the child if the mother consumed broccoli while pregnant. The 2018 ...

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

RUNX proteins act as regulators in DNA repair, study finds

August 15, 2018
A study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has revealed that RUNX proteins are integral to efficient DNA repair via the Fanconi Anemia (FA) ...


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.