Functional BRM promoter polymorphisms, pancreatic adenocarcinoma risk, and survival.
Bibliographic record
Abstract
222 Background: Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM -1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex (PMID:23524580). BRM suppression can be reversed pharmacologically (PMID: 21478905). Our group and others have reported associations with lung, head and neck, and hepatocellular cancer risk (PMIDs: 21478907, 23322154, 23359823). We have also reported associations with lung and esophageal cancer prognosis (ASCO 2013; abstr 11057 and 4077). In this analysis, we assessed risk and survival associations with pancreatic cancer. Methods: A population-based case-control study was conducted in Ontario with 623 histologically-confirmed pancreatic adenocarcinoma cases and 1192 age/gender distribution-matched controls (PMID: 23908141). Survival of cases was obtained through the Ontario Cancer Registry. Logistic and Cox proportional hazard regression models were fitted, adjusting for relevant covariates. Results: Median age was 65 years; 52% were male; 53% had received a curative resection; Stage I (8%), II (55%), III (14%), IV (23%); 79% received chemotherapy; 83% had died. In the risk analysis, the adjusted odds ratios were 1.01 (95%CI:0.1-2.0) and 0.96 (95%CI:0.7-1.3) for the homozygous variants of BRM-741 and BRM-1321, respectively, when each was compared to wildtype; adjusted odds ratio of double-homozygotes was 1.11 (95%CI:0.80-1.53) when compared to the double-wildtype. In contrast for the survival analysis, the hazard ratios (adjusted for age, stage, receipt of curative surgery, receipt of chemotherapy, and packyears) were 2.19 (95%CI: 1.9-2.5) for BRM-741 and 1.94 (95%CI: 1.7-2.2) for BRM-1321, per each unit increase in variant alleles. Compared with the double-wildtype, the adjusted hazard ratio for carrying no, one, and two homozygous (double-homozygous) variants were 2.14 (95%CI:1.6-2.8), 4.17 (95%CI:3.0-5.7), and 8.03 (95%CI: 5.7-11.4), respectively. Conclusions: Two functional promoter BRM polymorphisms were not associated with pancreatic adenocarcinoma risk, but are strongly associated with survival.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".