Photo Courtesy of the National Institute of Health

 

Characteristics of Lynch Syndrome

For those of us who have been diagnosed with cancer, time is a precious commodity. The time and distance from the scientist's lab bench to the patient's bedside must be shortened. ~ Larry Lucchino

 

Autosomal dominant inheritance pattern

Earlier average age of onset of colorectal cancer than in the general population (45 years in Lynch syndrome v. 63 years in the general population)

  • Proximal (right sided) colonic cancer predilection (70%-85% of colorectal cancers in Lynch syndrome are proximal to the splenic flexure)*

Accelerated carcinogenesis (tiny adenomas can develop carcinoma within 2-3 years in Lynch syndrome v. 8-10 years in the general population)

 

ยท        

 

 

 

MLH1-MSH2

1,2

MSH6

2

 

PMS2

3

Cancer

Gen Pop1

 

Risk

Avg Age

 

Risk

Avg Age

 

Risk

Avg Age

---------------

------------

 

-----------

-----

 

--------------

-----

 

----------

-----------

Colon

5.50%

 

40%-40%

44-81 yrs

 

10%-22%

54 yrs

 

15%-20%

51-66 yrs

Endometrium

2.70%

 

25%-60%

48-62 yrs

 

16%-28%

55 yrs

 

15%               

49 yrs

Stomach

<1%

 

1%-13%

56 yrs

 

<3%

63 yrs

 

6%*

70-73 yrs

Ovaries

1.60%

 

4%-24%

42.5 yrs

 

1%-11%

46 yrs

 

6%*

42 yrs

Hepatobiliary Tract

<1%

 

1.4%-4%

50-57 yrs

 

Unk

Unk

 

6%*

Unknown

Urinary Tract

<1%

 

1%-4%

54-60 yrs

 

1%               

65 yrs

 

6%*

Unknown

Small Bowel

<1%

 

3%-8%

47-49 yrs

 

Unk

54 yrs

 

6%*

59 yrs

Brain/CNS

<1%

 

1%-3%

50 yrs

 

Unk

Unk

 

6%*

45 yrs

Sebaceous Neoplasms

<1%

 

1%-9%

Unk

 

Unk

Unk

 

Unknown

Unknown

Pancreas4

<1%

 

1%-6%

Unk

 

1%-6%

Unk

 

Unknown

Unknown

 

 

1. Kohlman, W Gruber, SB

2012

 

www.genetests.org

 

1,2 Bonatel et al

Jama 2011

 

 

 

 

3 Sentel, et al

Gastroentrology 2008

 

 

4 Kastrinos et al

Jama 2009

 

 

 

 

* Starred Cancers combined = 6% Risk.

 

 

The Basics of Identification, Diagnosis and Management of Lynch Syndrome

Identification, Diagnosis and Management - Excellent Immediate Resource Guide for Physicians: Lynch Syndrome by Wendy Kohlman, MS and Stephen B. Gruber, MD, PhD, revised 9/20/2012

 

 

Other characteristics include:

 

  • Brain/CNS (1%-3% )

Sebaceous adenomas, sebaceous carcinomas and multiple keratoacanthomas in Muir-Torre syndrome (variant of Lynch syndrome)

Subset of Breast Cancer

  • Pathology of colorectal cancer is more often poorly differentiated, with an excess of mucoid and signet cell features, a Crohn-like reaction and an excess of infiltrating lymphocites within the tumor.

Increased survival from colorectal cancer

 

* In the MSH-6 mutation, most individuals have colorectal cancers located on the left side of the colon; including the descending colon, the sigmoid colon and the rectum, different from many of those with Lynch syndrome in which the cancers are proximal. There are more cases of endometrial cancer within those with an MSH-6 mutation.

 

Modified 5/18/2014