PSA/KLK3 AREI promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility
Why this work is in the frame
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Bibliographic record
Abstract
The proximal promoter of the kallikrein-related peptidase 3 gene (KLK3/PSA) contains a single-nucleotide polymorphism (G-158A) located within the second canonical half-site for the prostate-specific antigen (PSA) androgen response element 1 (AREI). Previous studies suggest that this polymorphism may be associated with higher PSA levels and increase prostate cancer risk. We have investigated the potential functional significance of this polymorphism and its association with prostate cancer susceptibility by genotyping the G-158A polymorphism in 209 men diagnosed with prostate cancer and 223 healthy control men in an Australian Caucasian population. Functional analyses of PSA AREI demonstrated that the A allele increased binding of AREI to the androgen receptor, as well as increasing transcriptional response to androgens. Association studies of the G-158A polymorphism demonstrated that men with an A/A genotype had a 3-fold increased risk for developing prostate cancer [95% confidence intervals (CIs) = 1.36-6.52] and men with an A/G genotype had a 2.4-fold increased risk (95% CIs = 1.23-4.81). Under a dominant model, the A allele conferred a 2.6-fold increased risk for prostate cancer (95% CIs = 1.37-4.96, P = 0.004). Taken together with the finding that the G-158A polymorphism is associated with an increased risk of prostate cancer in Australian men, our functional data suggest that the presence of the A allele in AREI may, in part, account for the altered PSA regulation seen in prostate cancer.
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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 it