Lynch Syndrome: Get the Facts about this Hereditary Cancer Syndrome - Answers to Frequently Asked Questions

Is there more than one genetic mutation that causes Lynch Syndrome and how do you test to know which one you have?

There is more than one genetic mutation. There are actually 5 genes that have been identified which if mutated would carry a diagnosis of Lynch syndrome. Within each of the 5 genes, multiple mutations have been identified in the gene sequence that are diagnostic for Lynch syndrome as well. It is best to discuss testing options with a genetic counselor or provider.

I am a mother of 2 kids, ages 13 and 11, and I have Lynch syndrome. What age should my kids get tested?

Response: They should get tested or consider testing between the ages of 20-25. That being said, every young adult is different and the ability to process the implications of testing is different for each person. If there are any questions or concerns about having your children tested seek out the support and guidance of a local cancer genetics genetic counselor and/or clinician.

What are the latest findings on the link between Lynch syndrome and uterine sarcoma?

Lynch syndrome is associated with uterine carcinomas. There have been case reports of persons with Lynch syndrome who have been diagnosed with a uterine sarcoma though it is uncommon. Since the link is not clear, if a woman presents with this type of tumor histology (uterine sarcoma) and has a past medical history and/or family history that suggest Lynch syndrome, I will typically recommend genetic testing.

I have Lynch Syndrome and get regular colonoscopies; can these be replaced by the new blood test or stool test for colon cancer?

Unfortunately, the study published for which this modality of testing was approved did not include persons with high risk of colorectal cancer or Lynch syndrome. There have been no follow up prospective studies comparing the use of the new blood test or stool test for colon cancer screening in the Lynch syndrome population.

My father passed away from stomach cancer – can this be due to Lynch syndrome?

The risk of stomach cancer can be inherited. There is a 6-13% lifetime risk of stomach cancer associated with Lynch syndrome. There are other inherited syndromes that can increase ones’ risk of stomach cancer. BUT, not all stomach cancers are inherited. A great majority are acquired. If you are interested to discuss or determine your risk of an inherited syndrome, I would recommend that you discuss this with your primary care provider and/or seek consultation for cancer genetics risk assessment and counseling.

There seems to be inconsistent data about whether breast cancer is related to Lynch syndrome. What should the screening protocol be?

Despite the recent suggestions of an increased risk for breast cancer in persons with Lynch syndrome, the data thus far does not support increased screening above average risk breast cancer screening recommendations or any impact on breast cancer treatment.

Do you think most doctors would recommend a complete hysterectomy for Lynch PMS2 mutation carriers who are done having kids but premenopausal and without a family history of ovarian cancer? 

Women with Lynch syndrome are at a reported lifetime risk of 4-12% for ovarian cancer. Families that carry a mutation in PMS2 have not consistently followed the same degree of cancer risk as Lynch syndrome patients with mutations in MLH1 or MSH2.

So my answer would be consideration for oophorectomy and hysterectomy after child bearing age is reached. This should be considered since current screening modalities for ovarian cancer screening are not reliable. If oophorectomy and hysterectomy is not accepted as an option, then I would encourage the individual to follow with an experienced gynecologist for ovarian and uterine screening.

I have Lynch syndrome – my mother was diagnosed with cancer in her ureter last year, and her sister had the same thing the year before. This appears to be uncharted territory for people with Lynch syndrome, or maybe it’s just our family. We are having a hard time nailing down a good protocol for catching this. Our doctors don’t seem to know much about Lynch association with bladder cancer – is there any research or established protocol?

The National Comprehensive Cancer Network (NCCN) and other professional societies recommend annual urinalysis starting at age 25-30 years in carriers of MLH1, MSH2 or EPCAM mutations. In families with your description we recommend regular follow up with a urologist to discuss and /or pursue cystoscopic surveillance.

How accurate is genetic testing? My husband was diagnosed with stage 4 colon cancer at age 47. We are not aware of any family history of cancer except lung cancer which was a result of his father smoking heavily. The doctor says it does not look to be genetic based on MSI and his age. Should he have genetic testing?

That is a tough question that is commonly asked. We currently stratify patients who should undergo genetic risk assessment and consideration for testing to patients who have particular clinical findings. There are limitations to our current diagnostic tools which include:

  • Tumor testing can be negative in a Lynch syndrome patient with an inherited genetic mutation.
  • Small families or early age of death in family members may limit our ability to adequately assess one’s risk and need for testing
  • Tumor testing only evaluates patients for the risk of Lynch syndrome and not other hereditary syndromes that may increase ones’ risk of developing colon cancer.

I was diagnosed with Lynch syndrome. I had genetic testing done but they couldn’t determine the exact mutation so no one else in my family could be tested. Is this common? I have an identical twin sister and we were told that she should also take precautions.

There are people with tumor testing that suggests Lynch syndrome who then have genetic testing that does not identify a mutation in one of the mismatch repair genes. In 30-40% of cases further testing demonstrates a non-genetic abnormality (a.k.a. an acquired genetic abnormality) that can explain this finding. In this scenario, clinical surveillance would follow one outlined for persons with average lifetime risk of colorectal cancer. In 60-70% of persons in this scenario, no other molecular cause is identified, and we designate this group as Lynch-like syndrome. It appears that the average age of diagnosis of cancer is similar to those with Lynch syndrome, however the lifetime risk of cancer development is not necessarily the same, and may actually be lower, than those with Lynch syndrome.

With that being said, since we as a scientific community, are still investigating this Lynch-like syndrome, standard guideline clinical surveillance for Lynch syndrome associated cancers/tumors should be initiated.

I have Muir-Torre Syndrome and have had lots of skin cancers removed & many internal cancers removed, I am 73. Two of my children have the same syndrome and are facing their second internal cancers. How rare is our cancer syndrome, which falls under Lynch syndrome?

Muir-Torre syndrome is considered a rare Lynch syndrome variant. It was coined to describe individuals with a combination of sebaceous neoplasms and one or more Lynch-associated cancers. It is a rare, though shares a similar risk of other Lynch-associated cancers as it is associated with mutations in the MLH1 and MSH2 genes. Therefore, screening regimens would follow standard guidelines established for other persons with Lynch syndrome.

Dr. Kimberly Perez is a Medical Oncologist at Dana-Farber Cancer Institute. She is a faculty member of the Gastrointestinal Disease Center and Center for Cancer Genetics and Prevention, and is part of the clinical faculty at Harvard Medical School. Dr. Perez attended medical school at the George Washington University School of Medicine in Washington, D.C., and completed her post-graduate training in Internal Medicine, Hematology and Oncology at Brown University Medical School. She recently joined the Dana-Farber faculty in November 2015, after 5 years of clinical practice as a GI oncologist at Rhode Island Hospital Comprehensive Cancer Center in Providence, to further develop her research and clinical interests in Gastrointestinal Cancer Care and Gastrointestinal Cancer Genetics.

The Ask the Expert Guest Series is not intended to be a substitute for healthcare professional medical advice, diagnosis, or treatment. Speak to your healthcare provider about any questions you may have regarding your health.