# Video research-update insert: Cigarette Smoking as a Major Cause of Lung Carcinoma

Editorial script and storyboard insert, 5 October 2026. No rendered video. Read alongside the original review; no new grade is announced.

## Narration

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.

In the 1996 study, benzo[a]pyrene-related adducts targeted major lung-cancer TP53 mutation hotspots. An adduct mechanism does not identify the initiating cause of each individual tumour. [P8832894]

In the 2004 study, eGFR-mutant adenocarcinoma was enriched among never smokers. Alternative causes are compatible with smoking causing a major share, not all tumours. [P15329413]

In the 2016 study, smoking correlated with several mutational signatures across cancer types. Different signatures and exposures can overlap; a tumour signature alone does not prove universal exposure specificity. [P27811275]

The next discriminating question is: Which molecular changes initiate cancer rather than accumulate later? Passenger mutation burden or promotion may accompany rather than define initiation. Exposure-resolved longitudinal airway sampling and lineage/driver analyses with matched controls; compare adduct, mutation and clonal expansion timing.

The timeline shows selected changes in evidence, not inevitable progress or proof of a single cause. The review’s archived grade remains unchanged; the depth of source reading is documented in the update.

## Storyboard and source locks

| Insert | Visual | Narration anchor | Sources |
|---|---|---|---|
| Opening | Claim and bounded update statement | First paragraph | Review claim and source ledger |
| Timeline 1996 | Dated study card with design, result and limit | Benzo[a]pyrene-related adducts targeted major lung-cancer TP53 mutation hotspots. | [P8832894](https://pubmed.ncbi.nlm.nih.gov/8832894/) |
| Timeline 2004 | Dated study card with design, result and limit | EGFR-mutant adenocarcinoma was enriched among never smokers. | [P15329413](https://pubmed.ncbi.nlm.nih.gov/15329413/) |
| Timeline 2016 | Dated study card with design, result and limit | Smoking correlated with several mutational signatures across cancer types. | [P27811275](https://pubmed.ncbi.nlm.nih.gov/27811275/) |
| G1 | Question → competing explanation → discriminating test | Which molecular changes initiate cancer rather than accumulate later? | [P8832894](https://pubmed.ncbi.nlm.nih.gov/8832894/), [P27811275](https://pubmed.ncbi.nlm.nih.gov/27811275/), [P15944214](https://pubmed.ncbi.nlm.nih.gov/15944214/) |
| G2 | Question → competing explanation → discriminating test | What determines persistent risk after cessation? | [P10926586](https://pubmed.ncbi.nlm.nih.gov/10926586/), [P15213107](https://pubmed.ncbi.nlm.nih.gov/15213107/), [P23343063](https://pubmed.ncbi.nlm.nih.gov/23343063/) |
| G3 | Question → competing explanation → discriminating test | How specific are tobacco-related signatures across co-exposures? | [P27811275](https://pubmed.ncbi.nlm.nih.gov/27811275/), [P8832894](https://pubmed.ncbi.nlm.nih.gov/8832894/), [P15329413](https://pubmed.ncbi.nlm.nih.gov/15329413/) |
| G4 | Question → competing explanation → discriminating test | Why do similarly exposed people develop different outcomes? | [P15329413](https://pubmed.ncbi.nlm.nih.gov/15329413/), [P15944214](https://pubmed.ncbi.nlm.nih.gov/15944214/), [P27811275](https://pubmed.ncbi.nlm.nih.gov/27811275/) |

## Editorial constraints

- Use the primary-source links shown above and keep the inference limit on screen with each milestone.
- Do not narrate an abstract check as complete-paper examination, a model result as human proof, or an unresolved inference as absence of all research.
- Preserve trial endpoint hierarchy, cohort reuse, correction notices and online/issue dates.
- Use original graphics made from this ledger. Publisher figure imagery has not been cleared or supplied for video reuse.
- Confirm any change in verdict through a separate documented HSEF review; this insert makes none.