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.
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Documents / Resources
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Quest Diagnostics MSH6 Genetic Insights Test [pdf] User Guide MSH6, MSH6 Genetic Insights Test, Genetic Insights Test, Insights Test, Genetic Insights |
