Impact of Gender and Parent of Origin on the Phenotypic Expression of Hereditary Nonpolyposis Colorectal Cancer in a Large Newfoundland Kindred With a Common MSH2 Mutation
Bibliographic record
Abstract
PURPOSE: This study was designed to provide precise estimates of death and cancer risks, by gender and parent of origin, in hereditary nonpolyposis colorectal cancer independent of mutation, geographic variation, and ascertainment bias. METHODS: A group of 12 families with a founder MSH2 mutation (nucleotide 943+3, A --> T) causing hereditary nonpolyposis colorectal cancer was identified in Newfoundland. Genetic testing was offered to those at 50 percent risk of inheriting the mutation. Medical records were reviewed to identify cancer types, age at onset of cancer, and age at death. Ascertainment bias was limited by analyzing only sibships with good ascertainment of genetic status (> or =50 percent of sibships had known genetic status). RESULTS: Of 302 family members with hereditary nonpolyposis colorectal cancer or at 50 percent risk, 151 (50 percent) were considered to be mutation carriers, 96 (32 percent) were mutation negative, and 55 (18 percent) were of unknown mutation status. By age 50 years, 72 percent of males and 72 percent of females who were hereditary nonpolyposis colorectal cancer mutation carriers had developed cancer. The age-related risks of colorectal cancer or of death of cancer were significantly higher in males than in females (relative risk = 2.8, P = 0.0001 and relative risk = 2.1, P = 0.01, respectively). The mutation was transmitted by the mother more frequently than the father. Females who inherited the mutation from their father had an increased risk of developing colorectal cancer (relative risk = 2.5, P = 0.05) and of dying of cancer (relative risk = 2.7, P = 0.04) compared with females who inherited the mutation from their mother. CONCLUSIONS: Investigation of large kindreds from the same geographic area who share the same MSH2 mutation and in whom family members have been identified with little ascertainment bias suggests that the risks for colorectal cancer and death of cancer are higher for male mutation carriers than for females and that females who inherit the mutation from their father are at higher risk of colorectal cancer than females who inherit the mutation from their mother.
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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".