Quest Diagnostics MSH6 Genetic Insights Test User Guide
- June 12, 2024
- Quest Diagnostics
Table of Contents
Genetic Insights: quick reference guide for healthcare providers
This guide is intended to facilitate a discussion between a provider and their patient.
Genetic Insights test results: Lynch syndrome
Key results
A pathogenic or likely pathogenic variant associated with Lynch syndrome was
found in the MSH6 gene.
People with Lynch syndrome have a significantly increased risk of developing
certain cancers, especially colon cancer and uterine cancer.
Next steps
Clinical recommendations | Resources |
---|
Genetic Insights is a screening test and is not intended for diagnosis. A
follow-up genetic test should be performed in a clinical setting before any
other action is taken.| Ready to order?
Check with your institution and/or patient’s insurance about the preferred
testing laboratory.
Blueprint Genetics® offers offers hereditary cancer testing. To confirm this
test result, targeted variant testing for the variant identified is
available. You can order a confirmation test here: Blueprint
Genetics/TVT
Have questions?
Call 1.866.GENE.INFO (1.866.436.3463) to speak to a specialized Quest genetic
counselor or
geneticist available to healthcare providers to discuss test selection and
results.
Refer your patient to a genetic counselor specializing in hereditary cancer.|
Your patient can schedule a 1-on-1 remote genetic counseling session through
their online
Genetic Insights Cancer Risk Report at no additional cost.
Genetic counselors can provide counseling onthe implications of this test
result and next steps for your patient.| To find a genetic counselor with
expertise in hereditary cancer practicing in your patient’s area
for an in-person session, please visit
FindAGeneticCounselor.NSGC.org
Patient conversation starters:
Patient conversation starters summarize the preceding information in plain
language to support meaningful conversations between you and your patient.
FindAGeneticCounselor.NSGC.org
Your Genetic Insights test is a screening test. The next step is to have your
result confirmed with a second genetic test.
It’s also important that you talk with a genetic counselor. Genetic counselors
are experts in genetics and can help you understand this result and potential
next steps.
You can access a genetic counselor through your Genetic Insights dashboard at
no additional cost to you, and we can discuss a referral to a local genetic
counselor.
Lynch syndrome is caused by DNA variants in certain genes.
People with Lynch syndrome have a higher than typical chance of developing
certain cancers, especially colon cancer and uterine cancer. Not everyone with
Lynch syndrome will develop cancer.
People with Lynch syndrome should have cancer screenings earlier in life and
more often than typical. This increases the chance that if cancer develops,
it’s detected as early as possible.Lynch syndrome runs in
families.
That means the DNA variants that cause Lynch syndrome can be inherited or
passed down from parents to their children. Your close relatives, like your
parents, full siblings, and children, have a 50% (or 1 in 2) chance of having
the same DNA variant. Other relatives might also have the same DNA variant.
Sharing these results with your family is important so family members can
decide if they want to have genetic testing for Lynch syndrome.
What is Lynch syndrome?
Lynch syndrome is a hereditary cancer predisposition syndrome characterized by
a higher-than-average lifetime risk of certain cancers and, typically, an
earlier age of onset. Colon cancer in men and women and uterine cancer in
women are the most common.
Risk for other types of cancer may also be increased.
Lynch syndrome is primarily associated with DNA variants in the MLH1, MSH2,
MSH6, PMS2, and EPCAM genes.
People with Lynch syndrome are recommended to undergo more frequent cancer
screening, typically starting at an earlier age than in the general
population.
See the Management options section for more detail.
What this result means for family members
Family members may have the same DNA variant. The DNA variant was most likely
inherited from a parent. Full siblings and children have a 50% chance of
having this variant.
In people with a confirmed DNA variant associated with Lynch syndrome, cascade
genetic testing for other family members 18 and older may help inform their
risks and screening protocols.
Children of biological parents who both have a DNA variant in MSH6 are at risk
for having a genetic condition called constitutional mismatch repair
deficiency (CMMRD).
A genetic counselor can help determine the most appropriate testing options.
Therefore, it is strongly recommended that people share their results with
their biological relatives and reproductive partners.
Cancer risk
Select estimated cancer risks in people with a confirmed variant in the MSH6 gene compared to the general population are included below. Individual cancer risks may be higher or lower depending on the specific variant identified, in addition to personal health history and family health history.
Cancer type
|
Approximate lifetime risk with MSH6 variant
|
Approximate lifetime risk in the general population
---|---|---
Males and females:
Colon| Up to 44%1,2,4| 4.2%5
Assigned female at birth:
Endometrial| Up to 46%1,2,4| 3.1%5
Ovarian| Up to 11%2| 1.3%5
Associated cancers and risks may change over time as medical research advances.
Management options
There are options for cancer prevention and early detection for people with Lynch syndrome. Clinical guidelines from the National Comprehensive Cancer Network© (NCCN©) in people with Lynch syndrome and no personal history of an associated cancer include 5:
Cancer type| Guidelines for people with the MSH6 variant detected|
Patient conversation starters:
---|---|---
Colon| Colonoscopy, starting at age 30-35, or 2-5 years prior to the earliest
colon cancer diagnosis in the family| It’s recommended that people with Lynch
syndrome have cancer screenings earlier and more often than typical. This way,
cancer is more likely to be caught in the early stages when it’s most
treatable. In fact, colon cancer can even be prevented if pre-cancerous
colon polyps are found and removed during a colonoscopy. If your Lynch
syndrome result is confirmed, it’s important to work with the right special-
ists—like a medical oncologist or gastroenterologist—to find cancer
screening and risk- reducing options that are right for you.
Colonoscopy should be repeated every 1-3 years
Endometrial| Consider risk-reducing hysterectomy on an individual basis
Consider endometrial biopsy every 1-2 years starting at age 30-35
Ovarian| Consider risk-reducing salpingo-oophorectomy on an individual basis
Gastric and smabowel| Upper GI surveillance with upper endoscopy starting at
age 30-40 or earlier based on family history
Repeat every 2-4 years or more frequently based on history
Other| Other cancer screenings or risk-reduction options beyond typical
recommendations may be considered based on personal health history and family
health history
See NCCN® for complete recommendations. Guidelines and recommendations may
change over time.
If the test result is confirmed, local centers of excellence in hereditary
cancer should be consulted for further clinical management. To locate a
genetics center or specialty clinic, please visit the American College of
Medical Genetics and Genomics at https://www.acmg.net/ACMG/Directories.aspx
Additional resources
The following patient advocacy groups have additional information and
resources about Lynch syndrome:
AliveandKickn:
AliveAndKickn.org
Facing Our Risk of Cancer Empowered (FORCE):
FacingOurRisk.org
References
-
Baglietto L, Lindor NM, Dowty JG, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. Journal of the National Cancer Institute.
2010;102(3):193–201. doi:10.1093/jnci/djp473 -
Dominguez-Valentin M, Sampson JR, Seppälä TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in medicine: official journal of the American College of Medical Genetics. 2020;22(1):15-25.
doi:10.1038/s41436-019-0596-9 -
Idos G, Valle L. Lynch Syndrome. February 4, 2004. Updated February 4, 2021. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews® [Internet].
University of Washington, Seattle; 1993-2022.
www.ncbi.nlm.nih.gov/books/NBK1211/ -
Møller P, Seppälä TT, Bernstein I, et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut. 2018;67(7):1306-1316. doi:10.1136/gutjnl-2017-314057
-
National Comprehensive Cancer Network© . Genetic/Familial High-Risk Assessment: Colorectal (Version 2.2022). NCCN Guidelines® . Accessed December 20, 2022.
www.nccn.org
This information is not a substitute for medical advice, diagnosis, or
treatment. The diagnosis or treatment of any disease or condition may be based
on personal history, family history, symptoms, a physical examination,
laboratory test results, and other information considered important by a
healthcare provider.
Individuals should talk with a healthcare provider about the meaning of
genetic test results and before stopping, starting, or changing any medication
or treatment.
Genetic Insights is a test developed and performed by Quest Diagnostics. The
test results are not diagnostic and do not determine overall chances of
developing a disease or health condition. The tests are not cleared or
approved by the US Food and Drug Administration.
QuestDiagnostics.com
Quest, Quest Diagnostics, any associated logos, and all associated Quest
Diagnostics registered or unregistered trademarks are the property of Quest
Diagnostics.
All third-party marks—® and ™—are the property of their respective owners. ©
2023 Quest Diagnostics Incorporated. All rights reserved. MI11781 3/2023
References
- Lynch Syndrome Hereditary Cancer | Aliveandkick'n
- FORCE - Facing Hereditary Cancer Empowered home page
- Home
- Home | Quest Diagnostics
- Genetic health screening | Quest Diagnostics
- Lynch Syndrome Hereditary Cancer | Aliveandkick'n
- Lynch Syndrome - GeneReviews® - NCBI Bookshelf
- Targeted Variant Testing - Blueprint Genetics
- Home
- Directories
- FORCE - Facing Hereditary Cancer Empowered home page
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