Browsing by Author "Chan, Carlos"

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    CHEK2 Founder Variants and Thyroid Cancer Risk
    (Mary Ann Liebert, 2024) Brock, Pamela; Liynarachchi, Sandya; Nieminen, Taina T.; Chan, Carlos; Kohlmann, Wendy; Stout, Leigh Anne; Yao, Song; La Greca, Amanda; Jensen, Kirk E.; Kolesar, Jill M.; Salhia, Bodour; Gulhati, Pat; Hicks, J. Kevin; Ringel, Matthew D.; Medical and Molecular Genetics, School of Medicine
    Background: Germline pathogenic variants in CHEK2 are associated with a moderate increase in the lifetime risk for breast cancer. Increased risk for other cancers, including non-medullary thyroid cancer (NMTC), has also been suggested. To date, data implicating CHEK2 variants in NMTC predisposition primarily derive from studies within Poland, driven by a splice site variant (c.444 + 1G>A) that is uncommon in other populations. In contrast, the predominant CHEK2 variants in non-Polish populations are c.1100del and c.470T>C/p.I157T, representing 61.1% and 63.8%, respectively, of all CHEK2 pathogenic variants in two large U.S.-based commercial laboratory datasets. To further delineate the impact of common CHEK2 variants on thyroid cancer, we aimed to investigate the association of three CHEK2 founder variants (c.444 + 1G>A, c.1100del, and c.470T>C/p.Ile157Thr) on NMTC susceptibility in three groups of unselected NMTC patients. Methods: The presence of three CHEK2 founder variants was assessed within three groups: (1) 1544 NMTC patients (and 1593 controls) from previously published genome-wide association study (GWAS) analyses, (2) 789 NMTC patients with germline exome sequencing (Oncology Research Information Exchange Network [ORIEN] Avatar), and (3) 499 NMTC patients with germline sequence data available in The Cancer Genome Atlas (TCGA). A case-control study design was utilized with odds ratios (ORs) calculated by comparison of all three groups with the Ohio State University GWAS control group. Results: The predominant Polish variant (c.444 + 1G>A) was present in only one case. The proportion of patients with c.1100del was 0.92% in the GWAS group, 1.65% in the ORIEN Avatar group, and 0.80% in the TCGA group. The ORs (with 95% confidence intervals [CIs]) for NMTC associated with c.1100del were 1.71 (0.73-4.29), 2.64 (0.95-7.63), and 2.5 (0.63-8.46), respectively. The proportion of patients with c.470T>C/p.I157T was 0.91% in the GWAS group, 0.76% in the ORIEN Avatar group, and 0.80% in the TCGA group, respectively. The ORs (with CIs) for NMTC associated with c.470T>C/p.I157T were 1.75 (0.74-4.39), 1.52 (0.42-4.96), and 2.31 (0.58-7.90), respectively. Conclusions: Our analyses of unselected patients with NMTC suggest that CHEK2 variants c.1100del and c.470T>C/p.I157T have only a modest impact on thyroid cancer risk. These results provide important information for providers regarding the relatively low magnitude of thyroid cancer risk associated with these CHEK2 variants.
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    General Surgery Education Across Three Continents
    (Elsevier, 2017) McIlhenny, Craig; Kurashima, Yo; Chan, Carlos; Hirano, Satoshi; Domínguez-Rosado, Ismael; Stefanidis, Dimitrios; Surgery, School of Medicine
    Surgical education has seen tremendous changes in the US over the past decade. The Halstedian training model of see one, do one, teach one that governed surgical training for almost 100 years has been replaced by the achievement of the ACGME competencies, milestones, entrustable professional activities (EPAs), and acquisition of surgical skill outside the operating room on simulators. Several of these changes in American medical education have been influenced by educators and training paradigms abroad. In this paper, we review the training paradigms for surgeons in the UK, Japan, and Mexico to allow comparisons with the US training paradigm and promote the exchange of ideas.