October 2008

Genetic Testing Key to Detecting Lynch Syndrome

Jonathan Terdiman, M.D.
Director of Gastrointestinal Cancer Prevention Program at UCSF

Amie Blanco, M.S., C.G.C.
Gordon and Betty Moore Endowed Counselor of Gastrointestinal Cancer Genetics
Cancer Risk Program at UCSF

Hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome, accounts for more than 3 percent of all colorectal cancer and is associated with an increased risk of endometrial, ovarian and other extracolonic cancers.

Commercial testing and evaluation for gene mutations associated with Lynch syndrome is widely available and cost-effective. It provides information critical to the future health care of both the cancer patient and their family members. Awareness and understanding of a patient's cancer risk can motivate individuals to seek appropriate medical surveillance, such as regular and consistent colonoscopies and check-ups at earlier ages. This coupled with state-of-the-art hereditary cancer risk testing and counseling and comprehensive education can lead to cancer prevention, early detection, and ultimately, to saved lives.

Nevertheless, most Lynch syndrome gene carriers are not identified. There are a number of factors that contribute to the low detection rate of Lynch syndrome, including the failure of nearly half of oncologists to document a comprehensive family history and for those who do, to refer appropriate patients for genetic evaluation. All clinicians, including primary care physicians, play an important role in identifying high-risk individuals by recording patient family histories and providing appropriate follow-up care and referrals for members of families with Lynch syndrome.

Cancer Risk

The estimated risk for colorectal cancer in those with gene mutations associated with Lynch syndrome is 70 percent by age 70. Colorectal cancer patients with Lynch syndrome have an estimated 40 percent risk of developing a second primary colorectal cancer within seven years of the first tumor. Women with Lynch syndrome have a 40 percent to 60 percent estimated lifetime risk for endometrial adenocarcinoma.

Studies also have consistently reported modest, increased risks for cancers of the stomach, ovary, urinary tract, hepatobiliary tract, brain, small intestine, skin and pancreas.

Screening and Testing

Patients should be screened or tested for Lynch syndrome if they are:

  • Newly diagnosed with colorectal or endometrial cancer — The first step in Lynch syndrome diagnosis is evaluating the tumor for molecular features associated with the syndrome (microsatellite instability). When a tumor is not available for screening, DNA testing can be offered if clinical presentation is strongly suggestive of Lynch syndrome.

  • Diagnosed with more than one Lynch-syndrome-related cancer — Patients diagnosed with multiple cancers associated with Lynch syndrome including colorectal, endometrial, ovarian, gastric, small bowel, upper urinary tract, hepatobiliary tract, pancreas, brain and sebaceous neoplasia of the skin.

  • From a family with history of colorectal or endometrial cancer — People with two or more relatives with colorectal or endometrial c ancer, particularly if one was affected before age 50.


Patients with a known or suspected genetic mutation associated with Lynch syndrome or who are at risk based on a documented mutation in their family should have a medical medical history and examination with detailed review of systems, education and counseling regarding Lynch syndrome every year beginning at age 20.

In addition, they should undergo the following surveillance:

  • Colorectal Cancer — Colonoscopy every one to two years, starting at age 20 or 10 years younger than the youngest age at diagnosis in the family, whichever comes first.

  • Endometrial Cancer — There are no background data on the sensitivity or specificity of routine endometrial cancer screening. However, given the high risk of developing endometrial cancer in women with Lynch syndrome, the following are recommended:

    • Endometrial biopsy every year beginning at age 25 to 30. An endometrial biopsy is also necessary in women with Lynch syndrome who report interim abnormal symptoms such as irregular vaginal bleeding or post-menopausal bleeding.
    • Transvaginal ultrasound for endometrial and ovarian cancer every year beginning at age 25 to 30.
    • Serum CA-125 blood test to screen for ovarian cancer every year beginning at age 23 to 30.

Automatic Screening at UCSF

The UCSF Cancer Risk Program, the largest and most comprehensive genetic testing center for cancer in Northern California, has screened over 3,000 people for Lynch syndrome and tested 300 for the condition. Now, in conjunction with the Gastrointestinal Cancer Prevention Program, patients with colorectal and endometrial cancer tumors are automatically screened for Lynch syndrome by a pathologist at the time of their surgery for colorectal or endometrial cancer.

The screening includes microsatellite instability analysis and immunohistochemistry for the mismatch repair proteins associated with Lynch syndrome. Patients who screen positive are then referred for genetic counseling and testing.

If a patient with colorectal cancer tests positive for Lynch syndrome, it may be recommended to remove the majority of the colon at the time of surgery, which would reduce the risk of developing another primary colorectal cancer tumor from 40 percent to 1 percent. Likewise, female patients may also want to consider having their uterus and ovaries removed to prevent the occurrence of endometrial and ovarian cancer associated with Lynch syndrome.

Health care professionals skilled in genetic testing, counseling and cancer risk can help patients decide which option is the best for them.

For more information, contact the Physician Referral Service at UCSF Medical Center:
Phone (888) 689-UCSF or (888) 689-8273
Email referral.center@ucsfmedctr.org

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