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Lynch syndrome: Lifetime Risk of Colorectal and Endometrial Cancers

A new study estimates the lifetime risks for colorectal and endometrial cancer in people with a genetic mutation for Lynch syndrome. The analysis was controlled to avoid bias and overestimating risk.

Even after adjusting for possible bias, lifetime risks for both cancers was high and the need for special surveillance was critical.

In 147 families with diagnosed Lynch syndrome (hereditary nonpolyposis colon cancer or HNPCC) there were 638 cases of colorectal cancer and 155 cases of endometrial cancer. All families had a mismatch repair (MMR) gene mutations (55 MLH1, 81 MSH2, and 11 MSH6).

For men in the study:

  • There was a 66 percent lifetime risk of colorectal cancer.
  • Median age at diagnosis was 42.
  • Highest lifetime risk was for men with an MLH1 mutation.

For women studied:

  • There was a 43 percent risk of colorectal cancer.
  • Median age at diagnosis of colorectal cancer was 47.
  • Lifetime risk for endometrial cancer was 39 percent.
  • Median age for endometrial cancer diagnosis was 47.5 years.
  • Risk for either colorectal or endometrial cancer was 73 percent.

Elena Stoffel, MD,MPH, and her colleagues concluded,

Lifetime risks of CRC and EC in mismatch repair gene mutation carriers are high even after adjusting for ascertainment. These estimates are valuable for patients and providers; specialized cancer surveillance is necessary.

Another study in Canada that analyzed risk for colorectal cancer for families in Ontario with Lynch Syndrome found a 60 percent risk by age 70 for men and  a 47 percent risk for women.  Men who carried a MLH1 gene had a 67 percent risk, while women had a 35 percent risk.  By age 90 risk of having colorectal cancer increased to 81 percent for men and 72 percent for women.

Carriers of the MLH1 gene had a fairly consistent increase of risk over the general population over their lives.  They were about 5 times more likely to get colorectal cancer at any age.  However, relative risk decreased for MSH2 carriers.  At age 30, they were thirteen times more likely to have cancer, decreasing to about 5 percent at age 70.

SOURCES:  Stoffel et al., Gastroenterology, published online July 18, 2009.

Choi et al., Hereditary Cancer in Clinical Practice, published online August 23, 2009.

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