Cytochrome P450 17A1 and Catechol <i>O</i>-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland
Bibliographic record
Abstract
PURPOSE: Lynch syndrome is a cancer predisposition syndrome which includes colon cancer. It is caused by inherited defects in DNA mismatch repair genes. Sporadic colon cancers are influenced by exogenous hormones (e.g., postmenopausal hormones); we hypothesized that polymorphisms which influence endogenous hormones would therefore modify age at colon cancer onset among Lynch syndrome mutation carriers. EXPERIMENTAL DESIGN: We genotyped 146 Caucasian Lynch syndrome mutation carriers for a 5'-untranslated region polymorphism in cytochrome P450 17A1 (CYP17; c.-34T-->C) and an exon 4 polymorphism in catechol O-methyltransferase (COMT; c.472G-->A); 50 mutation carriers had developed colon or rectal cancer at last contact. We used chi(2) tests to assess differences in counts. Kaplan-Meier survival curves and Cox proportional hazard models assessed age at onset of colorectal cancer stratified by CYP17 and COMT genotypes. RESULTS: Homozygous carriers of the CYP17 C allele were diagnosed with colorectal cancer 18 years earlier than homozygous carriers of the T allele. Hazard ratios identified that, relative to homozygous carriers of the T allele (T/T), carriers of one copy (T/C) and two copies (C/C) of the rare allele were, respectively, at 1.9-fold and 2.9-fold increased the risk of colon cancer at any age. The COMT rare allele suggested a nonstatistically significant trend of decreased colon cancer risk. CONCLUSIONS: This study showed that a polymorphism in CYP17 (c.-34T-->C) modifies age at onset of Lynch syndrome. Because of the high risk of colorectal cancer among this group, knowledge of the CYP17 genotype is warranted for genetic counseling and risk assessment. Future work should assess polymorphisms associated with steroid hormones in Lynch syndrome mutation carriers.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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".