A genetic analysis of the French Canadian population in search of evidence in favour of novel breast cancer susceptibility genes
Bibliographic record
Abstract
Germline mutations in the genes, BRCA1 and BRCA2 have been implicated in hereditary breast cancer (HBC) and hereditary breast and ovarian cancers (HBOC). A large-scale multi-center genetic linkage analysis revealed that while linkage to BRCA1 and BRCA2 was evident in the majority of HBOC families, the large proportion of HBC families remained unaccounted for by either of these genes. These findings supported the hypothesis that other novel breast cancer susceptibility genes could account for the unexplained clustering of female breast cancer cases in the HBC families. Previous studies have identified common BRCA1 and BRCA2 mutations in the French Canadian (FC) population. The objective of this thesis was to establish the contribution of BRCA1 and BRCA2 mutations to the HBC and HBOC families in the FC population of Quebec. Mutations were identified in 96 of 224 (43%) families that met our inclusion criteria of at least three verified cases of breast cancer diagnosed below 65 years of age or ovarian cancer. An additional 13 novel mutations were added to the FC mutation spectrum including the BRCA2:3398delAAAAG mutation which was identified in eight independent families. Haplotype sharing of closely related alleles in the carriers of this novel BRCA2 mutation suggested that the mutation was introduced by a common ancestor. Although the FC population was more heterogeneous than originally expected five common mutations accounted for 84% of the mutation carrier families. The BRCA1/BRCA2 phenotype was further defined to include metachronous bilateral breast cancer. In addition, 38 mutation-negative families were identified that were phenotypically indiscernible from the BRCA
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".