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Hoonsung Choi, Jung Ah Lim, Hwa Young Ahn, Sun Wook Cho, Kyu Eun Lee, Kyung Won Kim, Ka Hee Yi, Myung-Whun Sung, Yeo-Kyu Youn, June-Key Chung, Young Joo Park, Do Joon Park, and Bo Youn Cho


With the recent increasing rates of screening for thyroid cancer, the cancers now tend to be smaller and less aggressive than those that are diagnosed when presented with symptoms, suggesting changes in the clinical validity of conventional prognostic factors for outcomes. We performed the retrospective study to identify the secular trends in the prognostic factors of thyroid cancer.


We used medical records of 3147 patients diagnosed with papillary thyroid cancer (PTC) at the Seoul National University Hospital Thyroid Cancer Clinic between 1962 and 2009.


During the median 5.1-year follow-up, the overall recurrence rate was 13.3%, and male sex, tumor size, lymph node (LN) involvement, and extrathyroidal extension (ETE) were the significant prognostic factors for recurrence. Thyroid cancer-specific mortality was 1.4%, and the associated prognostic factors were older age, male sex, and LN involvement. For tumor recurrence, the hazard ratio (HR) for male sex decreased from 2.809 (95% CI, 1.497–5.269) in the pre-1989 period to 1.142 (95% CI, 0.736–1.772) in the post-1999 period. The pathologic characteristics, such as tumor size, LN involvement, and ETE, showed similar or increasing HRs over the time periods. For cancer-specific mortality, the HR for male sex decreased from 6.460 (95% CI, 1.714–24.348) in the pre-1990 period to 0.781 (95% CI, 0.083–7.379) in the post-1999 period.


The risk for poor outcomes in PTC associated with male sex decreased over time; in contrast, the risk associated with pathologic characteristics remained the same or increased over time. These trends might be associated with recent changes in the characteristics of patients with thyroid cancer.

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Emily Cottrell, Claudia P Cabrera, Miho Ishida, Sumana Chatterjee, James Greening, Neil Wright, Artur Bossowski, Leo Dunkel, Asma Deeb, Iman Al Basiri, Stephen J Rose, Avril Mason, Susan Bint, Joo Wook Ahn, Vivian Hwa, Louise A Metherell, Gudrun E Moore, and Helen L Storr


Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1).

Design and methods

Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions.


Both cohorts were enriched for class 3–5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts.


Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.