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In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. A Correction to this article was published on 20 July A Correspondence to this article was published on 05 December This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer.
We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants.
After validation the cohorts were merged providing participants and 51, follow-up years. There were prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate.
Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers. Lynch syndrome LS results from pathogenic variants in the mismatch repair MMR genes and is the most common hereditary cancer syndrome, affecting an estimated 1 in individuals.
