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Lynch syndrome (LS) is the most frequent cancer predisposition syndrome affecting the colon and rectum. A pathogenic variant (PV) disrupting one of the mismatch repair (MMR) genes is responsible for the disease. The spectrum of tumors in LS is heterogeneous and includes cancer of the colon and rectum (CRC), endometrium, ovaries, stomach, small bowel, urinary tract, bladder, pancreas, and skin. Knowledge of the phenotypic variation of patients with LS, the type and frequency of PVs, and cascade testing studies in the Latin American population is limited. The present study aims to recognize the PVs in MMR genes, describe the phenotype in Mexican-Mestizo patients and their relatives, and identify the acceptance rate of cascade testing of relatives at risk. We included 40 carriers of a MMR gene PV and 142 relatives that developed a LS-related neoplasm. Patients' clinical data, number, and type of malignancies were obtained from their medical records. Amsterdam I-II, Bethesda criteria, and PREMM5® predictive model score were estimated. Available immunohistochemistry (IHC) reports were analyzed. Relatives at risk were determined from index cases pedigrees. The distribution of MMR gene mutations among 40 probands was: MLH1 (67.5 %) , MSH2 (22.5 %) , MSH6 (7.5 %), and PMS2 (2.5 %). Out of the 182 LS cases, 58 % exhibited the LS phenotype before age 50. The most common tumor was CRC, followed by endometrial cancer in women and gastric cancer in males. We found a 90.0 % concordance between the IHC and germline PV. The most frequent PV in our sample was MLH1 c.676C > T, occurring in 1/6 index cases. All probands disclosed their molecular test result to their family. Out of the 451 asymptomatic relatives at risk, 28.2 % underwent germline testing. Our results highlight the importance of conducting germline genetic studies in LS since it allows the establishment of appropriate cancer screening, risk-reducing measures, and genetic cascade testing among relatives at risk. Interestingly, we observed a significantly higher prevalence of the c.676C > T variant in MLH1, probably a singular characteristic of the Mexican-Mestizo population. New strategies to facilitate accurate communication between index cases and relatives should be implemented to improve the cascade testing acceptance rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Highly trafficked health websites are major sources of information, but the quality of their musculoskeletal information has not been thoroughly evaluated or their authorship characterized., Objectives: To review information about common musculoskeletal conditions on highly trafficked websites and characterize their credibility, authorship, accuracy of information (as compared to treatment guidelines), and consistency with best practice recommendations., Design: Systematic review., Methods: We reviewed the top 15 most highly trafficked health websites, identified by web traffic data. Information about 7 common musculoskeletal conditions was identified and data extracted. Credibility was assessed using the Trust It or Trash It? tool, author backgrounds were identified, accuracy was determined by comparing webpage treatment recommendations to guidelines or systematic reviews, and consistency with best practice recommendations was assessed., Results: Of 1760 webpages screened, 87 were reviewed. Less than half (44.8%, 39/87) had appropriate sources listed, but 65.5% (57/87) were updated in the previous 5 years. Journalists authored most webpages (55.2%, 48/87). Physician involvement was mostly editorial, and they often lacked expertise in musculoskeletal conditions. Information accuracy was concordant with guidelines for 49.4% (43/87) of webpages, but varied by condition. About half of best practice recommendations were followed (49.1%, 427/870). Pages were unlikely to mention psychosocial factors (16.1%, 14/87), limitations of imaging (18.4%, 16/87), or staying at work (4.6%, 4/87)., Conclusions: Popular health websites scored poorly for credibility, accuracy, and consistency with best practice recommendations for musculoskeletal conditions. Authorship, bias, and unsupported information are potential sources of inaccuracies that should be addressed in future by these websites., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown., Methods: We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53-1.79, p = 7.2 × 10 -33 ) and synchronous (OR 1.33, 95% CI 1.19-1.50, p = 2.4 × 10 -6 ) breast cancers., Conclusions: This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)