Epidemiology, cessation, experimental carcinogenesis and tumour signatures converge on smoking as a major causal route. Remaining research questions concern individual susceptibility, persistent injury and attribution among overlapping exposures, rather than whether the overall causal relationship exists.
This dated addendum adds selected evidence and tests that could resolve the remaining questions. It does not regrade the archived review.
Each question identifies a limit in the checked evidence. A missing search result alone does not establish a gap in the entire field.
Competing explanation: Passenger mutation burden or promotion may accompany rather than define initiation.
Discriminating test: Exposure-resolved longitudinal airway sampling and lineage/driver analyses with matched controls; compare adduct, mutation and clonal expansion timing.
Competing explanation: Pre-existing clones, epigenetic injury and age-related processes may outlast exposure.
Discriminating test: Prospective cessation cohorts with repeated airway/genomic measurements, verified exposure and lung-cancer incidence; account for competing mortality.
Competing explanation: Ambient carcinogens, second-hand smoke or shared repair processes may create overlapping patterns.
Discriminating test: Component-resolved exposure measures and independent tumour cohorts; quantify attribution uncertainty rather than assigning cause from a single signature.
Competing explanation: Genotype, histology, airway biology and competing exposures may modify risk.
Discriminating test: Large prospective dose-resolved cohorts with predefined effect modifiers and mechanistic validation; separate susceptibility from necessity or sufficiency.
Electronic publication dates are used where recorded, with issue years shown separately. This is a selected chronology, not a claim of scientific priority or independent replication for every entry.
A foundational report examined smoking and lung carcinoma.
What it cannot establish: Metadata-only anchor in this update; its original numerical results were not re-examined.
A separate report examined smoking in confirmed lung-carcinoma cases.
What it cannot establish: Metadata-only anchor; hospital selection and recall remain design limits.
Benzo[a]pyrene-related adducts targeted major lung-cancer TP53 mutation hotspots.
What it cannot establish: An adduct mechanism does not identify the initiating cause of each individual tumour.
Stopping smoking greatly reduced subsequent lung-cancer risk.
What it cannot establish: Nonrandomized cessation and historical exposure reconstruction require consideration.
Long follow-up associated persistent smoking with higher mortality and cessation with benefit.
What it cannot establish: Repeated reports from this cohort are not independent replications; generalization beyond its population requires other cohorts.
EGFR-mutant adenocarcinoma was enriched among never smokers.
What it cannot establish: Alternative causes are compatible with smoking causing a major share, not all tumours.
Long-term smoke exposure induced lung cancer with molecular changes.
What it cannot establish: Species, dose and exposure conditions limit direct human quantitative extrapolation.
Continued smoking reduced life expectancy; earlier cessation provided larger benefit.
What it cannot establish: All-cause mortality estimates must not be relabelled as lung-cancer-specific effects.
Smoking correlated with several mutational signatures across cancer types.
What it cannot establish: Different signatures and exposures can overlap; a tumour signature alone does not prove universal exposure specificity.
Case-specific Consensus records assisted gap discovery, chronology and targeted paper questions. Shared template wording about an amyloid-specific Deep follow-up is not evidence of a Deep run for this topic; the dated source records establish the actual use and access limits. Primary identifiers, selected abstract passages, correction notices and available primary-body passages were cross-checked. Generated absence cells, duplicate milestones and unsupported access claims were rejected.
Primary abstract/metadata checked. Additional Consensus full-text details remain provider-reported because a separately readable body was unavailable in this update.
This focused addendum does not establish 50–70 complete primary Methods/Results examinations per review. Baseline reading receipts and scores retain their original scope.
Selected full-text checks: 0; abstract checks: 7; metadata-only anchors: 2. Complete-paper examinations credited in this update: 0.
New enrichment: HSEF v5.3 causal distinctions. Archived scorecard schema: 5.4; retained as recorded.
PMID 14772469 · DOI 10.1136/bmj.2.4682.739
Metadata only: historical anchor. Identifier, title and publication metadata checked; original results not re-examined.
PMID 15415260 · DOI 10.1001/jama.1950.02910390001001
Metadata only: historical anchor. Identifier, title and publication metadata checked; original results not re-examined.
PMID 8832894 · DOI 10.1126/science.274.5286.430
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
PMID 10926586 · DOI 10.1136/bmj.321.7257.323
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
PMID 15213107 · DOI 10.1136/bmj.38142.554479.AE
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
PMID 15329413 · DOI 10.1073/pnas.0405220101
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
PMID 15944214 · DOI 10.1093/carcin/bgi150
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
Linked notices: Correction (identifier unavailable in this record)
Linked notice presence was checked in the primary record; its scientific impact was not verified in this update.
PMID 23343063 · DOI 10.1056/NEJMsa1211128
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
PMID 27811275 · DOI 10.1126/science.aag0299
Selected abstract passages checked. Primary record and selected abstract passages checked; no complete-paper appraisal credited.
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