Pathogenic variants (disease-causing) in both copies of the MSH3 gene have MSH3-associated polyposis syndrome, which is associated with an increased risk of colorectal polyps and colorectal cancer, but the exact lifetime risk numbers are not well defined because this condition is rare. Management of MSH3–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. MSH3 variants are not known to be more common in the Ashkenazi Jewish population.
As noted above, MSH3-associated polyposis exhibits autosomal recessive inheritance. This means that both parents must be carriers of an MSH3 pathogenic variant to have a 25% chance to have a child with the condition; a carrier means that an individual has a single MSH3 pathogenic variant. Carriers, to the best of our knowledge, do not have an increased of cancer or polyps. If an individual has MSH3-associated polyposis, the chance their children could have it depends on the genetic make-up of the other parent.
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Written December 2025
