Thanks to Angelina Jolie, who went public in a 2013 New York Times editorial about her decision to undergo a preventive double mastectomy, most of us are familiar with the BRCA1 and BRCA2 genes. In fact, the actress’s announcement about her positive BRCA status, which significantly upped her risk of developing breast – and ovarian – cancer, sparked a marked rise in genetic testing among women with family histories of both diseases.
But Lynch Syndrome, an even more prevalent inherited cancer syndrome, has largely slipped under the radar.
Lynch Syndrome affects 1 in 300 people, according to Amanda Hamblett, CGC, MS, a genetic counselor at Middlesex Health in Middletown. Individuals with Lynch Syndrome have a significantly increased risk of developing several types of cancer, particularly colon and endometrial cancer. Whereas most people have a 4.5 percent risk of developing colon cancer, for example, that risk can jump to as high as 82 percent in people with Lynch Syndrome. The risk of endometrial – or uterine – cancer (the endometrium is the lining of the uterus) can rise from 2.7 percent in the general population to as high as 60 percent in a woman with Lynch.
“We actually have genes that function in our body to fix mistakes in our DNA and protect us from developing cancer,” explains Hamblett. “We have two copies of every gene – one from Mom and one from Dad – and if we happen to inherit from one of our parents a gene that is supposed to protect us from cancer that is not working, we don’t get that protection, so it puts us at increased risk for developing cancer within our lifetime.” The mutations associated with Lynch Syndrome occur in genes that are supposed to be protective.
Hamblett notes that not all people with Lynch Syndrome develop cancer. But because Lynch elevates the risk of several types of cancer, she says, it’s important to know whether you are a candidate for testing. “We’re all at risk for something,” she says. “The ability to know what you’re at risk for allows you to act on it and head off that risk. It’s a really amazing piece of information to have.”
Who’s at risk?
As with BRCA testing, family history is a key factor in determining who should be tested for Lynch Syndrome. “We look at family – and personal – history of colon or endometrial cancer, early age at diagnosis (before 50) for those and other cancers, and multiple primary cancers in one person or in a family,” says Kelly Watrous, MS, CGC, another genetic counselor at Middlesex Health who works closely with Lynch Syndrome families. Lynch also significantly raises the risk for prostate and ovarian cancers, she says. Other Lynch-linked diseases include cancers of the stomach, urinary tract, pancreas and brain.
Still, notes Watrous, colon and endometrial cancers are the hallmark of Lynch. For this reason, all newly-diagnosed colon and endometrial cancer patients at Middlesex are specially screened for Lynch Syndrome.
There are five genes associated with Lynch. When the pathology department evaluates tissue after a biopsy, they test for the presence of the proteins made by these genes. “If any of the proteins are absent,” Hamblett explains, “it may mean that one copy of one of those five genes is not working.” If the screening test is positive, she says, she would suggest that patients go on to get diagnostic or genetic testing, which will look at the actual genes to see if there is an aberration. Genetic testing can be done on blood or saliva but is typically done via blood test at Middlesex. A person’s risk profile is contingent on which of the five genes is affected.
Because there is overlap between different inherited cancer syndromes – mutations in both Lynch Syndrome and BRCA 1 and 2 genes raise the risk of ovarian cancer, for example – specialists at Middlesex will often screen individuals for several different syndromes at once. Thanks to advances in genetic testing over the past decade, this is now an option, says Hamblett.
“About six or seven years ago, the testing changed to allow labs to look at multiple genes at the same time,” she says.
“This next generation screening allows us to look at anywhere from 35 to 80 genes at once, whereas 10 years ago we had to test for one gene at a time.” So if a patient comes in with a family history of ovarian cancer, she adds, they can look at the BRCA genes, the Lynch genes, and others like RAD51C, RAD51D, and BRIP1, which also raise the risk of ovarian cancer.
You have Lynch Syndrome – now what?
“There are specific clinical things we do once we know you have Lynch,” says Middlesex Health colorectal surgeon J. Michael Parker. “We recommend a colonoscopy every year, an upper endoscopy (in which a tube is inserted through the mouth to view inside the stomach and intestines) every three to five years, and a urinalysis every year to look for urinary tract cancer.”
Doctors may also do physical and neurologic exams to assess the brain, and skin exams because of a rare type of skin cancer that can be linked to Lynch Syndrome. Some doctors will do transvaginal ultrasounds or a CA 125 blood test to screen for ovarian cancer, though Hamblett notes that data hasn’t shown these measures to be that useful in identifying early stage ovarian cancers. The best way to manage the increased risk of ovarian cancer, she says, is to have the ovaries removed.
Sometimes, Dr. Parker says, if he finds out a colon cancer patient has Lynch Syndrome, rather than doing a smaller colon surgery, he might take out more of the colon to lower the patient’s risk of developing future cancers. But first he will test for other potentially associated cancers. If a patient also had uterine cancer, for example, he could operate on both organs concomitantly.
Lynch Syndrome also increases the risk of polyps in the colon; indeed, most colon cancers arise as a result of polyps that turn malignant. “In regular populations, it takes a long time for a normal colon to develop a polyp and for the polyp to become a cancer – 10 to 15 years in most people,” notes Dr. Parker. “In people with Lynch, that process is much faster, taking only two to three years.” But while people with Lynch become cancerous faster, they actually do better, Dr. Parker says, because they are monitored more closely and are able to have those polyps removed before they can become cancerous. For this reason, colonoscopies start much earlier in people with Lynch – at age 20 to 25. “The idea is to start before they start developing polyps,” says Watrous.
Why genetic counseling is so important
There are so many complexities to Lynch Syndrome, says Watrous. It is connected to several different genes and affects the risk for several types of malignancies. Genetic counseling can help patients determine whether testing is right for them, and what steps to take should they test positive. “It’s all about risk reduction,” she says, “so we can encourage prevention and early detection in our patients and their families.”
Though only 10 percent of cancer is hereditary, Hamblett says, those who inherit Lynch Syndrome are at increased risk not only for getting colon or endometrial cancer, but also for getting multiple primary cancers. Their family members could also be at risk, and genetic counseling can help determine who in the family could benefit from undergoing genetic testing.
“The way that inheritance works is that each sibling or child of that person would have a 50/50 chance to have also inherited Lynch Syndrome and to have an increased risk of whatever the cancer is in that family.” That’s why it’s so important for people to know their family medical history.
Some people opt not to get tested, even after counseling, Watrous concedes. Some don’t want to know they are at increased risk – perhaps they wouldn’t do anything differently or they don’t have children or siblings who could benefit from the knowledge – or maybe they are worried about genetic discrimination. Also, adds Hamblett, people who have just been diagnosed with cancer and are trying to make decisions about treatments might be too overwhelmed to add anything else onto their plates.
But, as Dr. Parker puts it, “Being forewarned is being forearmed. If you know ahead of time you have Lynch Syndrome, you may never get cancer, but you have the knowledge to go out there and prevent it – more so than the average person. What a privilege to know you can prevent something.”
Lori Miller Kase is a freelance writer living in Simsbury.
Photography by Tony Bacewicz