Clinicopathologic and genetic features of young patients with colorectal cancer
Bibliographic record
Abstract
Colorectal cancer (CRC) is the 3rd most common cancer in Canada, often occurring at older ages. While early-onset CRC can be suggestive of an inherited syndrome, the underlying genetic cause remains unexplained in many of these young individuals. Clinicopathologic features along with genetic and family information were collected on individuals diagnosed with CRC ≤35 years old identified through the Familial Gastrointestinal Cancer Registry in Toronto, Canada. 441 individuals from 353 families were identified, and to-date, medical records confirmed 254 diagnoses, which were included for analysis. Ninety patients (35.4%) had germline mutations in self or kin (31 MSH2, 36 MLHI, 1 MSH6, 3 PMS2, 24 APC, 2 MYH biallelic and 1 BRCA2). Individuals were classified into six categories; (a) 74 had Lynch syndrome (LS) confirmed by germline mutation or tumour deficiency (b) 4 had constitutional mismatch repair-deficiency (CMMR-D) (c) 61 had polyposis (mutation positive, >25 adenomas or hamartomatous polyps), (d) 6 met Family X criteria, (e) 7 had inflammatory bowel disease (IBD), and (f) 102 were unclassified (NOS), with 69 of these individuals having MSS and/or IHC intact tumours. On average, patients with CMMR-D presented younger, with a mean age of 14 years old at diagnosis. 65.2% of patients with LS presented with a proximal tumour (65.2%) compared with the polyposis (10.2%) and NOS (34.4%) groups. In contrast, 83% of polyposis patients and 65.5% of NOS patients presented with distal colon or rectal cancers. Family history was significant for the majority of LS patients with 54 of 73 (74%) meeting Amsterdam I or II criteria. Two of the 7 patients with IBD, and 15 of 98 NOS patients also met Amsterdam I/II criteria, as opposed to the CMMR-D families where none met these criteria. Six LS patients presented with sporadic CRC, as did approximately 25% of polyposis patients and 59.2% of the NOS patients. Cancer site differs between individuals ≤35 years with LS, polyposis and NOS CRC. Greater than 1/3 of patients presented with no significant family history of CRC. While the majority of patients diagnosed with CRC ≤35 have a known hereditary CRC syndrome or risk predisposition, 69 of 221 (31.2%) of individuals appear to have no recognizable syndrome.
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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 | 0.001 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".