ICARE Social Media Post March 2020

MLH1: Cancer Risks and Risk Management

Gene: MLH1

Cancer Risks and Management (per NCCN version 3.2019):


Endometrial cancer risk: Elevated at 43%-57% – Consider risk-reducing hysterectomy.

Ovarian cancer risk: Elevated at 5%-20% – Recommend risk-reducing bilateral salpingo-oophorectomy (removal of ovaries and fallopian tubes).

Breast cancer risk: Elevated at 12%-17% – Manage same as general population.

Men and Women:

Colorectal cancer risk: Elevated at 46%-49% – Recommend colonoscopy every 1-2 years starting at age 20-25.

Gastric cancer risk: Elevated at 5%-7% – Consider upper endoscopy every 3-5 years beginning at age 40 for select MLH1 carriers (see NCCN for details).

Pancreatic cancer risk: Elevated at 6% – Consider MRI/MRCP or endoscopic ultrasound for MLH1 carriers with a family history of pancreatic cancer in first-degree relative.

Urothelial cancer risk: Elevated at 0.2%-5% – Consider urinalysis annually starting at age 30-35 for MLH1 carriers with a family history of urothelial cancer.


Prostate cancer risk: Elevated at 0%-17% – Manage same as general population.

Inheritance: Autosomal dominant, thus parents, full siblings, and children have a 50% risk for the gene mutation. If both parents have an MLH1 mutation, the child is at risk for autosomal recessive Constitutional mismatch repair deficiency (CMMRD) syndrome.

Family Testing: At-risk family members should consider genetic counseling and genetic testing. For adult-onset conditions, recommend delaying genetic testing on minors until they are at least 18 years old.

Reproductive Considerations: Option for preimplantation genetic diagnosis (PGD) may be available to ensure future generations do not inherit the known gene mutation. PGD is a procedure available for certain gene mutations to screen the embryo prior to achievement of pregnancy.

Check out the full management guidelines by creating a FREE account at https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf and https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

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