Double-strand breaks repair in lymphoblastoid cell lines from sisters discordant for breast cancer from the New York site of the BCFR
Bibliographic record
Abstract
Unrepaired DNA double-strand breaks (DSBs) may have serious consequences for cells by inducing chromosomal aberrations, thereby increasing genetic instability and cancer risk. One's capacity to repair DSB is therefore an important factor to consider when estimating cancer risk. We assessed DNA end-joining (EJ) capacity in cell lines derived from sisters discordant for breast cancer to determine if individual differences in DSB repair are a significant risk factor. We used an in vitro phenotypic assay on nuclear extracts from lymphoblasts of 179 subjects including 86 cases and 93 controls. EJ activity was functionally estimated as the ability of extracts to join together monomers of the plasmid pUC18 linearized either with sticky (EcoRI) or blunt ends (HincII). Mean percentage of EJ capacity was slightly lower in cases than controls, both for EcoRI (cases 27.9 +/- 11.1; controls 29.6 +/- 10.7, P = 0.28) and HincII substrates (cases 28.8 +/- 12.2; controls 30.6 +/- 13.0, P = 0.36); however, no significant differences were observed. Categorizing EJ capacity into tertiles and using the highest activity as the referent, we observed elevated associations for each tertile of decreased repair [Odds ratio (OR) = 2.20, 95% confidence interval (CI) = 0.77-6.22 and OR = 4.22, 95% CI thinsp;= 1.22-14.0, P = 0.02], respectively, for EcoRI. Results were not statistically significant for HincII (OR = 1.37, 95% CI = 0.51-3.70 and OR = 2.32, 95% CI = 0.57-9.38, P = 0.24). These data suggest that individual differences in EJ capacity may represent a risk factor predisposing women to breast cancer.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".