Abstract LB-333: A case-parent-triad approach in assessing risk of osteosarcoma associated with genetic variation in insulin-like growth factor 1/growth hormone axis genes: a Children's Oncology Group (COG) study
Bibliographic record
Abstract
Abstract Osteosarcoma (OS) is a rare malignant bone tumor with an overall incidence rate of 4.6 cases per million children aged 0-19 years in the United States. OS incidence peaks sharply in adolescence coinciding with the pubertal growth spurt. While the etiology of OS is largely unknown, its distinctive age-incidence pattern suggests that growth and development is crucial in the genesis of OS. Prior studies have suggested that variants in genes in the insulin-like growth factor 1 (IGF1)/growth hormone (GH) axis pathway are associated with OS. We assessed this hypothesis by examining 307 single nucleotide polymorphisms (SNPs) in 12 genes from this pathway (GHRH, GH1, GHR, GHRHR, IGF1, IGF1R, IGF2, IGF2R, IGFBP1, IGFBP3, IGFBP6, AND IGFALS) in a case-parent-triad study of cases and their biological parents. The sample included 229 complete triads and 56 dyads diagnosed during 2008-2011 at Children's Oncology Group institutions. Buccal cell samples were collected via the Oragene kit (DNA Genotek, Ottawa, Ontario) and returned by mail; genotyping was conducted by Sequenom iPLEX Gold method. We used log-linear models to estimate relative risks (RR) and 95% confidence intervals (CI) associated with transmitting one or two copies of the variant compared to no copies. After Bonferroni correction, 2 SNPs in IGFBP1 (rs10231774: RR = 1.44 and 0.07 for 1 and 2 vs. 0 copies, respectively; p < 0.001) and IGFALS (rs2575352: RR = 2.82 and 0.22 for 1 and 2 vs. 0 copies, respectively; p < 0.001), both in the upstream coding regions of IGF pathway genes, were significantly associated with OS incidence. These results confirm previous findings that variation in the IGF1/GH axis influence OS risk and further support the axis’ biologically and epidemiologically plausible role in OS development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-333. doi:1538-7445.AM2012-LB-333
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".