Lead in biological samples and site-specific cancer risk associated mortality: a systematic review
Bibliographic record
Abstract
We plan to conduct a comprehensive review of existing meta-analyses and original studies that focused on the association between Pb measured in biological samples (blood, urine, or nails) and cancer-specific risk or mortality in non-occupationally exposed individuals. We will search PubMed and EMBASE using the following search string: (lead OR Pb) AND (metal or element) AND (cancer* OR malign* OR tumour OR tumor) AND (risk OR inciden* OR mortality). No temporal, geographic, or language restriction will be applied, as long as an English abstract was available to decide on eligibility. We will include original articles as well as meta-analyses that reported a measure of relative risk (RR; e.g. odds ratio, hazard ratio, risk ratio, standardized incidence and mortality ratios; for meta-analyses, summary RR obtained via either fixed or random effects models) and corresponding 95% confidence intervals (CI) for the association between Pb levels measured in biological samples (e.g. blood, urine, and nails) and the risk of cancer or cancer-related mortality, separately by body district or for cancer at any site. We will exclude articles in which the risk of developing (or dying from) cancer is studied exclusively in relation to any of the following: (a) estimated Pb dietary intake; (b) occupational exposure to Pb (e.g. via inhalation of Pb-containing dusts, fumes, or mists on the workplace); (c) Pb measured in air, water, soils, or other environmental media; (d) Pb levels determined in cancerous and non-cancerous tissues; (e) exposure to a mixture of multiple metals (and possibly non-metal pollutants) including Pb; (f) composite scores containing Pb as one of the items; and other. We will further exclude studies reporting the mean/median Pb levels among cases and controls (including standardized mean differences, SMD) but no RR estimate; those in which the study population was made up of cancer patients and the outcome of interest was patients’ survival or risk of recurrence; and studies having an ecological design. For the purpose of organizing and reporting the results of the literature search, we will group the different tumours according to their site and morphology, based on the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3), as follows: tumours of the head and neck (C00-C14 + C30-C32); tumours of the gastrointestinal system (C15-C26) as a whole or of the oesophagus and stomach (C15-C16), colon-rectum (C18-C20), liver and intrahepatic bile ducts (C22), gallbladder and extrahepatic bile ducts (C23), or pancreas (C25); lung (C34); blood and lymph nodes (C42 + C77); skin melanoma (C44); breast (C50); corpus uteri (C54); ovary (C56); prostate (C61); testis (C62); kidney (C64); bladder (C67); thyroid (C73); and cancers of any site and morphology (i.e. studies having as outcome the overall cancer incidence or mortality). For each of the above, we will include: (a) the most recent meta-analysis (if any existed), or more than one if they differed in terms of inclusion criteria (e.g. Pb measured in blood or in urine; including either prospective or retrospective studies; etc.) or methods of analysis (e.g. summary relative risk calculated for the comparison of the highest vs. lowest category of Pb levels, or reporting the results of dose-response analyses; having as outcome either cancer risk or cancer-related mortality; etc); (b) all original papers published after the most recent meta-analysis, or not included in it (in case of multiple studies with overlapping populations, e.g. cohorts analysed at different points in time, we considered the article based on the largest number of cancer cases or, in case of equal size, the most recent one). The quality and susceptibility to bias of original articles will be assessed by means of the Newcastle-Ottawa Scale (NOS), separately for studies having a prospective and retrospective design (i.e. cohort and nested case-control studies and, respectively, non-nested case-control studies).
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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 | 0.011 | 0.034 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.020 |
| Bibliometrics | 0.007 | 0.010 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".