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Lynch Syndrome - Symptoms

What are the cancer risks associated with Lynch syndrome?

Lynch syndrome is associated with a faulty (disease-causing) copy of MMR genes, namely MLH1, MSH2, MSH6, PMS2, and EPCAM.

Individuals who have Lynch syndrome (carriers) face an increased risk of cancers, but it does not mean that they will definitely develop cancer. Carriers face different cancer risks depending on which faulty gene they have.

Cancer risks associated with Lynch syndrome as compared to the general population^1-2
Cancer type	*MLH1 carrier risk*	*MSH2 & EPCAM carrier risk*	*MSH6 carrier risk*	*PMS2 carrier risk*	General population risk
Colorectal	46 - 61%	33 - 52%	10 - 44%	9 - 20%	5%
Uterus (endometrial) (females)	34 - 54%	21 - 57%	16 - 49%	13 - 26%	3%
Ovarian (females)	4 - 20%	8 - 38%	≤ 1 - 13%	1 - 3%	1.3%
Breast (females)	May be increased				13%
Prostate (males)	4 - 14%	4 - 24%	3 - 12%	5 - 12%	12%
Renal pelvis and/or ureter	0.2 - 5%	2 - 28%	0.7 - 6%	≤ 1 - 4%	–*
Bladder	2 - 7%	4 - 13%	1 - 8%	≤ 1 - 2%	2.4%
Gastric	5 - 7%	0.2 - 9%	≤ 1 - 8%	–*	0.9%
Small bowel	0.4 - 11%	1 - 10%	≤ 1 - 4%	0.1 - 0.3%	0.3%
Pancreas	6%	0.5 - 2%	1.6%	≤ 1 - 2%	1.6%
Biliary tract	2 - 4%	0.02 - 2%	0.2 - 1%	0.2 - 1%	0.2%
Brain	0.7 - 2%	3 - 8%	0.8 - 2%	0.6 - 1%	0.6%

*inadequate data
Note: The conditions associated with Lynch syndrome and their risk estimates may change as more information is available.

References
1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Colorectal. Version 1.2020. 2020 July 21; National Comprehensive Cancer Network.
2. Dominguez-Valentin, M. et al (2020). Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in Medicine, 22(1), 15–25. https://doi.org/10.1038/s41436-019-0596-9

Lynch syndrome increases the risk of cancer in both males and females.

The common cancers in Lynch syndome

Urinary tract
Stomach
Colorectal
Pancreas
Prostate
Ovary and Uterus

Other less common cancers associated with Lynch syndrome are hepatobiliary tract cancer, small bowel cancer, brain cancer, and sebaceous neoplasms (skin cancer).

There are other genes aside from MMR genes that increase the risk of colorectal cancer (e.g., APC, POLE, POLD1, PTEN, CHEK2, MUTYH, NTHL1, MSH3) as part of other genetic conditions. Genetic testing for colorectal cancer will usually include testing of such genes as well.