Management implications of a pathogenic or likely pathogenic variant in a Lynch syndrome gene*

Patient population	Intervention(s) that may be appropriate
Risk reduction
All individuals	Increased CRC surveillance (early initiation and increased frequency of colonoscopy) Possible aspirin chemoprevention after discussion of risks and uncertain benefit Surveillance upper endoscopy with visualization of the duodenum Helicobacter pylori testing and treatment if positive Possible screening urinalysis Possible annual skin examination Preconception counseling; some may opt for alternative reproductive technologies (donor gametes, IVF with PGT)
Females (in addition to surveillance and interventions for all individuals above)	Education regarding symptoms of endometrial and ovarian cancer Discussion of hysterectomy and rrBSO, typically done after childbearing is complete and/or at the time of CRC resection Discussion of transvaginal ultrasound, endometrial biopsy, and CA-125 testing for those who have not undergone hysterectomy and rrBSO Hormonal chemoprevention for those who are premenopausal and have not undergone hysterectomy and rrBSO
Males (in addition to surveillance and interventions for all individuals above)	In MSH2 and MSH6 carriers, discussion of prostate cancer screening by prostate-specific antigen test at age 40 and follow-up in a high-risk cancer screening clinic
Family members
First- and second-degree relatives	Genetic counseling and consideration of testing for adult at-risk relatives Cascade testing of their relatives if appropriate
Cancer management
Colorectal	More extensive surgery Possible use of cancer immunotherapy (eg, PD-1 inhibitor) as second-line option
Endometrial cancer	Management as for the general population Possible use of cancer immunotherapy (eg, PD-1 inhibitor) as second-line option
Other cancers	Management as for the general population Possible use of cancer immunotherapy (eg, PD-1 inhibitor) as second-line option

This table is intended as an information summary and should not take the place of the clinical judgment of the treating specialists. Refer to UpToDate topics on hereditary colorectal cancer syndromes for important information.

CRC: colorectal cancer; IVF: in vitro fertilization; PGT: preimplantation genetic testing; rrBSO: risk-reducing bilateral salpingo-oophorectomy; PD-1: programmed death 1; MMR: mismatch repair.

* Refers to a germline variant; includes variants in MMR genes MLH1, MSH2, MSH6, PMS2, and the EPCAM gene. Pathogenic or likely pathogenic variants in other MMR genes are very rare and management is individualized.

Graphic 122460 Version 7.0

خرید پکیج

Management implications of a pathogenic or likely pathogenic variant in a Lynch syndrome gene*