This genetic mutation increases the risk dramatically for several types of gynecologic cancers, but you've probably never heard of it. Here's when experts want women to know.

By Sarah Klein
September 14, 2018

By now, most women are well aware that genes play a role in the risk for certain cancers. Thanks in large part to Angelina Jolie and other celebrities speaking publicly about their own breast cancer diagnoses and preventive surgeries, just about everyone knows that a mutation of a gene called BRCA can be dangerous—even if we may not know all the scientific details.

But there’s a genetic mutation you might not have heard about that increases a woman’s lifetime risk of uterine, colon, and ovarian cancer quite dramatically: Lynch syndrome.

If you’re a carrier of this inherited mutation, you have a 40% to 60% chance of developing uterine (also called endometrial) cancer in your lifetime; a 40% to 60% chance of developing colon cancer at some point in life, and a 5% to 10% chance of ovarian cancer throughout your life as well. Compare these numbers to the risk for a woman without the gene mutation: 4% for colorectal cancer, 3% for uterine cancer, and 1% for ovarian cancer, according to data from the National Cancer Institute.

Errors in four specific genes are linked to Lynch syndrome: MLH1, MSH2, MSH6, and PMS2. These genes are involved in repairing cellular damage in DNA, explains Shannon Westin, MD, MPH, a gynecologic oncologist at the MD Anderson Cancer Center in Houston. When that cell repair doesn’t happen normally, the damage can lead to cancer, she says.

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When it was first discovered, Lynch syndrome was initially called hereditary nonpolyposis colorectal cancer. It was thought to mainly lead to colorectal cancer because—surprise, surprise—it was studied mostly in men, Dr. Westin says. Men with Lynch syndrome have a 60% to 80% chance of developing colorectal cancer in their lifetime. But when researchers studied women, they quickly discovered “astronomical rates” of colorectal and uterine cancers, she says, in addition to lower but still elevated rates of ovarian and some other rarer cancers.

Those cancers are, however, “entirely preventable,” says Douglas A. Levine, MD, director of gynecologic oncology at NYU Langone’s Perlmutter Cancer Center. “It’s important to identify people who are at risk and perform preventive surgery so they don’t have to get these cancers.”

So how do you know if Lynch syndrome could run in your family? And what does it take to prevent associated cancers? Read on.

Lynch syndrome symptoms

Even with advancements in screening and genetic testing, the majority of people diagnosed with Lynch syndrome are at a doctor's office because they already have cancer. You won’t exactly feel any different if you have Lynch syndrome; rather, a “symptom” of the genetic condition could be the cancer itself, especially at a younger than typical age, such as before 50.

Ideally, Lynch carriers would be identified before they ever get cancer. To find them, doctors recommend that people look into their family history. Possible telltale signs of Lynch can be a family history of colon, endometrial, or ovarian cancer, especially at younger ages. “We used to have a 3-2-1 rule,” explains Dr. Levine. “It’s not perfect, but as a guideline for illustrative purposes: If you have three family members with colon or endometrial cancer, two of whom are first-degree relatives to each other, and one is under 50, those people should have genetic testing for Lynch syndrome.”

But Dr. Westin warns that plenty of people with Lynch syndrome have no known family history, “so there’s still a high proportion we don’t identify.” She suspects this is in part because many families simply don’t talk about “down there” cancers.

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Lynch syndrome causes

Lynch syndrome is an "autosomal dominant" trait, meaning you only need one abnormal gene to get it. If one of your parents has Lynch syndrome, you have a 50% chance of having it too. Yet experts don't entirely understand why some people with Lynch syndrome go on to develop cancer and others don’t.

If Lynch syndrome is identified in your family tree, doctors might recommend that all your relatives get tested for the mutation. “We can check the whole family and prevent cancers,” Dr. Westin says. Those folks are often referred to as "previvors."

In general, it’s thought that between 1 in 500 and 1 in 1,000 people have Lynch syndrome, according to MD Anderson. Between 5% and 10% of all endometrial cancer cases are thought to be attributable to Lynch, experts say. And between 3% and 5% of colorectal cancer cases are due to Lynch, according to the U.S. National Library of Medicine’s Genetics Home Reference.

RELATED: How to Know If You Should Get a Genetic Test for Ovarian Cancer

Lynch syndrome screening

Colorectal and uterine cancer patients are often (if not always) screened for Lynch syndrome, Dr. Westin says, in hopes of preventing cancers in family members. Experts can look at tumor tissue samples under a microscope or evaluate DNA sequences to look for genetic mutations, says Konstantin Zakashansky, MD, director of gynecologic oncology at Mount Sinai West (called immunohistochemistry and microsatellite instability testing, respectively). Blood tests may also be used to confirm a diagnosis of Lynch syndrome, he adds.

People who don’t have cancer but may be Lynch carriers can be screened using genetic testing. This usually entails giving a blood or saliva sample and working with a genetic counselor to evaluate your risk, Dr. Westin says. (Some at-home genetic testing kits do include Lynch syndrome, but a genetic counselor can help you interpret your results.)

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Lynch syndrome treatment

If someone with Lynch syndrome has already been diagnosed with cancer, that cancer will need to be treated, of course. (There are now FDA-approved immunotherapy treatments for some Lynch-associated cancers, Dr. Levine adds.)

But if a Lynch carrier doesn’t have cancer, doctors turn toward preventive screenings and procedures. For starters, people with Lynch syndrome are screened for colon cancer with colonoscopies or other testing methods more frequently than people with an average risk of colon cancer. Women are screened for uterine cancer with a yearly endometrial biopsy, “which is an office procedure that’s slightly painful for just a minute or two that samples cells on the inside of the uterus,” Dr. Levine explains.

Of course, the only definitive way to prevent cancer in a specific organ is to have that organ surgically removed. And obviously, a colectomy (the removal of part or all of the colon), a hysterectomy (removal of the uterus), and an oophorectomy (removal of the ovaries) are major surgeries not to be taken lightly—especially, in the case of a hysterectomy, if you'd still like to become pregnant. “The standard for prevention is a hysterectomy once someone is done having children,” Dr. Levine says. It’s recommended to have the procedure by about age 40 to ensure cancer hasn’t developed yet, he adds.

Pregnancy, he continues, is itself preventive. “It’s a high-progesterone state,” he says. “It’s almost unheard of” to develop endometrial cancer while pregnant.

That's because endometrial cancer is driven by estrogen, Dr. Zakashansky explains. The hormone builds up the uterine lining, then progesterone sloughs it off—which gives women monthly periods. But when more lining builds up, there's more potential for cell mutations that lead to cancer. “If there’s a deficiency in the gene responsible for controlling abnormalities, that’s when things can go haywire,” Dr. Zakashansky says. For the same reason, progesterone IUDs may be protective, although more research is needed on this approach, Dr. Westin says.

If you think you could have Lynch syndrome based on a family history of ovarian or colorectal cancer, it's important to talk to a doctor about your risk. But don't panic: “The presence of the gene mutation is what puts you at risk," says Dr. Zakashansky. "It doesn’t mean you’re going to have cancer.”