Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018, Columbia University Medical Center
Credit: CC0 Public Domain

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 cancer by age 60.

The study, in collaboration with GeneDx, a genetic testing company, was published online today in Genetics in Medicine.

The two were previously known to cause Lynch syndrome, an inherited condition that raises the risk of colorectal, ovarian, stomach, and endometrial cancer. Lynch syndrome is the most common inherited cause of colorectal cancer, accounting for about 3 percent of newly diagnosed cases. One in 440 Americans has a gene variant that causes Lynch syndrome.

Researchers had suspected that Lynch syndrome genes may also cause . Some studies had found a link, whereas others had not.

"People with Lynch syndrome aren't thinking they may also be at risk for cancer," said Wendy Chung, MD, PhD, the Kennedy Family professor of pediatrics (in medicine) at Columbia University Irving Medical Center, clinical geneticist at NewYork-Presbyterian/Columbia, and the study's senior author. "Given the fact that genomic analysis is becoming more common in patients with a personal or family history of cancer, we have an opportunity to do more targeted breast cancer screening in women who carry any of the genes associated with risk for this disease."

The researchers analyzed a database of more than 50,000 women who had undergone multi-gene hereditary cancer testing between 2013 and 2015. Of these, 423 women had a mutation in one of the four genes that cause Lynch syndrome: MLH1, MSH2, MSH6, and PMS2.

Additional analyses revealed that women with a mutation in two specific Lynch syndrome genes—MSH6 and PMS2—had a two-fold higher risk of breast cancer compared to women in the .

Based on the incidence of cancer in the study population, the researchers calculated that about 31 to 38 percent of women with cancer-causing MSH6 and PMS2 variants will develop breast cancer, compared to around 15 percent of women in the general population.

"The new study suggests MSH6 and PMS2 should be added to the list of genes to screen for when there is a history of breast cancer," said Dr. Chung, who is also director of the clinical genetics program at NewYork-Presbyterian/Columbia. "Screening for these genes also would give these families potentially life-saving information to prevent colon cancer by encouraging individuals with the genes to increase the frequency of their colonoscopies."

Currently, testing for Lynch syndrome genes is generally only done when someone has a personal or family history of colon or uterine cancer.

Dr. Chung added, "Given that Lynch is not rare in the general population, this finding has the potential to impact tens of thousands of people in the U.S. and could change standard practice related to one of the most common predisposition syndromes."

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

More information: Maegan E Roberts et al, MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer, GENETICS in MEDICINE (2018). DOI: 10.1038/gim.2017.254

Related Stories

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. ...

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 ...

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

December 15, 2016
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 ...

High risk of colorectal, endometrial and Lynch syndrome cancers for MSH6 mutation carriers

December 22, 2009
People carrying the germ-line MSH6 mutation are at high risk by age 80 years for colorectal and endometrial cancers and any cancer associated with Lynch syndrome, according to a new study published online December 22 in the ...

Study identifies genetic mutations associated with cancer risk for hereditary cancer syndrome

June 5, 2011
(Medical Xpress) -- Among various genetic mutations for individuals with Lynch syndrome, a hereditary cancer syndrome that carries a high risk of colon cancer and an above-normal risk of other cancers, researchers have identified ...

Whole-population testing for breast and ovarian cancer gene mutations is cost effective

January 17, 2018
Screening the entire population for breast and ovarian cancer gene mutations, as opposed to just those at high-risk of carrying this mutation, is cost effective and could prevent more ovarian and breast cancers than the current ...

Recommended for you

Critical role of DHA on foetal brain development revealed

August 17, 2018
Duke-NUS researchers have found evidence that a natural form of Docosahexaenoic Acid (DHA) made by the liver called Lyso-Phosphatidyl-Choline (LPC-DHA), is critical for normal foetal and infant brain development, and that ...

Gene silencing critical for normal breast development

August 17, 2018
Researchers have discovered that normal breast development relies on a genetic 'brake', a protein complex that keeps swathes of genes silenced.

New algorithm could improve diagnosis of rare diseases

August 17, 2018
Today, diagnosing rare genetic diseases requires a slow process of educated guesswork. Gill Bejerano, Ph.D., associate professor of developmental biology and of computer science at Stanford, is working to speed it up.

Officials remove special rules for gene therapy experiments

August 16, 2018
U.S. health officials are eliminating special regulations for gene therapy experiments, saying that what was once exotic science is quickly becoming an established form of medical care with no extraordinary risks.

Genetic link discovered between circadian rhythms and mood disorders

August 15, 2018
Circadian rhythms are regular 24-hour variations in behaviour and activity that control many aspects of our lives, from hormone levels to sleeping and eating habits.

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

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.