Abstract 4739: Interactions between variants of angiogenesis pathway genes and reflux symptom, BMI, and smoking in esophageal adenocarcinoma susceptibility
Bibliographic record
Abstract
Abstract Esophageal adenocarcinoma (EA) is a complex malignancy that involves multiple genetic and environmental risk factors. Genetic polymorphisms in angiogenesis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with EA development. However, interactions among multiple factors in EA risk have not been well characterized. We conducted a case-only study to investigate gene-environment interactions among 145 functional/tagging SNPs of angiogenesis pathway genes, reflux, smoking, and BMI in 335 patients with EA. We used a two-stage approach to detect interactions: first, we applied random forest (RF) approach to select important interacting markers based on mean decrease in accuracy and mean decrease in GINI index; then we estimated the interaction odds ratios (ORinter) of RF selected interaction markers by case-only logistic regression, adjusting for covariates and false discovery rate (FDR). We identified twelve interaction markers that were significantly associated with EA risk (all FDR_Ps<0.05). Among them, six interaction markers, including reflux*rs2295778 (HIF1AN) (ORinter=2.27; 95% CI, 1.44-3.57), reflux*rs996999 (MMP1) (ORinter=1.80; 95%CI, 1.12-2.89), reflux*rs13337626 (TSC2) (ORinter=2.18; 95%CI, 1.15-4.12), BMI*rs2114039 (PDGFRA) (ORinter=2.06; 95%CI, 1.29-3.30), BMI*rs6554164 (PDGFRA) (ORinter=1.92; 95% CI, 1.20-3.08), and BMI*rs17708574 (PDGFRB) (ORinter=1.89; 95%CI, 1.12-3.18) were significantly associated with increased risk of EA. On the other hand, six interaction markers, including reflux*rs2519757 (TSC1) (ORinter=0.43; 95% CI, 0.21-0.83), smoking*rs2295778 (HIF1AN) (ORinter=0.45; 95%CI, 0.26-0.79), smoking*rs2296188 (FLT1) (ORinter=0.50; 95%CI, 0.28-0.87), BMI*rs2296188 (FLT1) (ORinter=0.41; 95%CI, 0.24-0.73), BMI*rs11941492 (KDR) (ORinter=0.52; 95%CI, 0.32-0.85), and BMI*rs17619601 (FLT1) (ORinter=0.26; 95%CI, 0.09-0.75) were significantly associated with decreased risk of EA. These findings suggest that variants in angiogenesis pathway genes, reflux, smoking, and BMI jointly contribute to EA development through gene-environment interactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4739.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".