From autoimmune inflammation to malignancy: causal genetic evidence for the rheumatoid arthritis (RA)-squamous cell lung cancer axis
Main finding · Squamous cell lung cancer, after matchingResult — go to the resultAdjusted odds ratio 2.415 95% CI 1.104–5.283Authors' conclusion
RA specifically increases squamous cell lung cancer (but not other subtypes) risk. Multivariable Mendelian randomization resolves the causal paradox caused by smoking confounding.
Study context
- Population
- Real-world cohort, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 2014–2024; GWAS summary data of European ancestry (RA N = 92,044; squamous cell lung cancer N = 63,053; smoking N = 111,752)clinical cohort
- Participants
- 8,867 participants
- Exposure
- RA vs non-RA; genetic liability to RA and squamous cell lung cancer
- RAn = 4,661
- Outcome
- Lung cancer subtypes (adenocarcinoma, squamous cell carcinoma, small cell carcinoma)
Methodological detailsevidence triangulation, 1:1 propensity score matching, single-centre, machine learning risk prediction, multivariable Mendelian randomization adjusted for smoking, LDSC
- Evidence triangulation
- 1:1 propensity score matching
- Single-centre
- Machine learning risk prediction
- Multivariable Mendelian randomization adjusted for smoking
- LDSC
Main finding
Squamous cell lung cancer, after matching
Adjusted odds ratio
2.415
95% CI 1.104–5.283
P = 0.027
RAvs Non-RA
adjusted OR 2.415 (95% CI 1.104–5.283); P = 0.027
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| Multivariable MR (adjusted for smoking): RA on squamous cell lung cancer | 1.02 (1.00–1.04) | P = 0.046 | |
| 0.512Odds ratio (log scale) |
| Outcome | Estimate | P value |
|---|---|---|
| Adenocarcinoma, after matching | P = 0.437 | |
| Small cell carcinoma, after matching | P = 0.564 | |
| Univariable MR: RA on squamous cell lung cancer (European)Apparent protective effect | OR 0.985 | |
| LDSC genetic correlation RA–squamous cell lung cancer | rg −0.019 | P = 0.806 |
Adenocarcinoma, after matching
- No significant association
Small cell carcinoma, after matching
- No significant association
Machine learning prediction of overall lung cancer (22 clinical features)
- AUC (limited predictive ability)
- 0.57-0.68
Original publication
From autoimmune inflammation to malignancy: causal genetic evidence for the RA-squamous cell lung cancer axis. Arthritis Res Ther. Published 1 December 2025. doi:10.
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