Effects of Glutamate and Aspartate on Prostate Cancer and Breast Cancer: A Mendelian Randomization Study
Bibliographic record
Abstract
Abstract Background: Respectively, prostate cancer and breast cancer are the second most and most commonly diagnosed cancer in men and woman, and they account for major cancer-related deaths world-wide. Special attention aiming to find potentially effective early detection of, and intervention strategies against, prostate cancer (PCa) and breast cancer need to be paid.Objective: Utilizing Mendelian randomization (MR), we aimed to estimate how genetically predicted glutamate and aspartate levels affected prostate and breast cancers development. Methods: Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to predict the serum levels of glutamate and aspartate from the publicly available genome-wide association studies (GWASs), which were conducted to associate genetic variations with blood metabolite levels using comprehensive metabolite profiling in 1,960 adults and the glutamate and aspartate we chosen were two of 644 metabolites. The summary statistics for the largest and latest GWAS datasets for prostate cancer (61,106 controls and 79,148 cases) were from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium and datasets for breast cancer (113,789 controls and 133,384 cases) were from Breast Cancer Association Consortium (BCAC). The analyses were performed through two-sample MR method. Results: Serum level of aspartate was positively associated with prostate cancer (Effect = 1.043; 95% confidence interval, 1.003 to 1.084; P = 0.034) and breast cancer (Effect = 1.033; 95% confidence interval, 1.004 to 1.063; P = 0.028); however, glutamate was neither associated with prostate cancer and breast cancer. The potential causal associations were robust to the sensitivity analysis.Conclusions: Our study found that the level of serum aspartate could serve as a risk factor that contributed to the development of prostate and breast cancers. Efforts detailing the underlying mechanism(s) would be extremely valuable in early assessment/diagnosis and strategizing clinical intervention of both cancers.
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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 | 0.013 | 0.023 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".