Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome
Bibliographic record
Abstract
BACKGROUND: Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers. METHODS: We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan-Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period-specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population. RESULTS: Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97). CONCLUSION: Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate 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 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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".