Revised Table 3, Absolute Risks of Colorectal Cancer (CRC) for Carriers of Pathogenic Variants in Hereditary CRC Syndromes, to state the risk as 10% to 56% by age 75 years in patients with Lynch syndrome, depending on the gene involved.
Added text about a retrospective study that reported standardized incidence ratios of breast cancer that were calculated by comparing observed breast cancer frequencies in a population of 423 women with pathogenic or likely pathogenic variants in mismatch repair genes with those in the general population. The authors reported a statistically significant age-standardized risk of breast cancer for MSH6 carriers and PMS2 carriers (cited Roberts et al. as reference 331). A critical limitation of this study was the excess of breast cancer cases in the overall referral population as well as the known high background population prevalence of MSH6 and PMS2 germline pathogenic variants.
Revised Table 14, Practice Guidelines for Diagnosis and Colon Surveillance of Lynch Syndrome, to state that recommendations for individuals with biallelic mismatch repair deficiency are available from the U.S. Multi-Society Task Force on Colorectal Cancer (cited Durno et al. as reference 440).
Added text to state that because pathogenic variants in SMAD4 and BMPR1A are known to account for juvenile polyposis, clinicians have referred young patients with fewer than five polyps for genetic testing; a study conducted on 77 patients with a total of 84 polyps found that the yield of genetic testing in patients with a limited number of polyps is minimal; of the germline variants detected, none were classified as definitely pathogenic or likely pathogenic (cited Jelsig et al. as reference 578).
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