The effect of two BRM promoter variants on the risk of stage I/II upper aerodigestive tract cancers.
Bibliographic record
Abstract
10522 Background: BRM is a key subunit of the chromatin remodeling complex SWI/SNF and a putative tumor suppressor gene that is silenced in 15-20% of many solid tumors (PMID 15722796). Evidence suggests that it is epigenetically regulated, as two BRM promoter insertion variants (BRM-741 and BRM-1321) may lead to gene silencing by recruiting histone deacetylases. The presence of both homozygous BRM-741 and BRM-1321 highly correlate with loss of BRM expression and function in lung tumors, while increasing smoking-related lung cancer by two-fold (PMID 21478907). Also, the pharmacologic reversal of epigenetic changes of BRM offers a potential novel therapeutic approach (PMID 21478905). We assessed whether these BRM variants are associated with the risk of upper aerodigestive tract cancers, focusing on Stage I/II tumors that would most benefit from new screening and prevention strategies. Methods: BRM was genotyped by qPCR using TaqMan probes. 1,008 controls were matched to 595 cases by frequency distribution based on age, gender and smoking status. Multivariate logistic regression generated adjusted odds ratios (aOR). Results: The 595 cases were: 115 esophageal, 278 lung, and 202 head and neck cancers. 51% were adenocarcinomas; 60% were Stage I. The frequency of homozygozity was: BRM-741, 26%; BRM-1321, 23%; both variants, 15%. In the combined analysis, there was significant correlation between malignancy and homozygous BRM-741 (aOR 1.91 (95%CI 1.3-2.4); p=0.001) or BRM-1321 (aOR 1.94 (95%CI 1.4-2.7; p=3x10E-4). Being homozygous for both BRM variants carried an even greater risk (aOR 2.45 (95%CI 1.6-3.9); p=1x10E-5). This correlation was similar for adenocarcinomas (aOR 2.53 (95%CI 1.4-4.2); p=6x10E-4) and squamous cell carcinomas (aOR 2.33 (95%CI 1.3-4.4); p=8x10E-4). The increased cancer risk was also similar between these subgroups: head and neck, esophageal and lung cancers; Stage I and II patients; smokers and non-smokers. Conclusions: The two homozygous BRM variants increase the risk of early stage upper aerodigestive tumors by more than two-fold independent of smoking status. BRM promoter variants and their potential epigenetic effect may be early events in the evolution of these cancers.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.006 | 0.004 |
| 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 | 0.001 |
| 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".