# Association between cardiovascular disease and non-melanoma skin cancer: The mediation effect of obesity and inflammation

**Authors:** Xin Zhang, Zhe Gao, Ying Miao, Xin-Gang Wu

PMC · DOI: 10.1371/journal.pone.0343992 · PLOS One · 2026-03-23

## TL;DR

This study finds that cardiovascular disease increases the risk of non-melanoma skin cancer, with obesity and inflammation partially explaining the link.

## Contribution

The study identifies obesity and inflammation as mediators between cardiovascular disease and non-melanoma skin cancer.

## Key findings

- CVD is a risk factor for NMSC (OR: 1.83, 95% CI: 1.01 ~ 3.34, p = 0.048).
- SIRI, BMI, and WWI partially mediate the CVD-NMSC relationship (p < .001).
- Weight loss and inflammation control may reduce CVD and NMSC prevalence.

## Abstract

Although the association between CVD and various cancers has been extensively studied, its relationship with NMSC remains ambiguous. Previous studies have shown that cardiovascular disease (CVD) is an independent risk factor for tumorigenesis. However, the relationship between CVD and non-melanoma skin cancer (NMSC) is unclear. The aim of this study is to investigate the potential relationship between CVD and NMSC and whether obesity and inflammation mediate the association.

7424 participants from the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018 were included. Diagnosis of CVD and NMSC was determined by questionnaire combined with self-reported. Inflammatory markers and obesity indices assessed were SIRI, SII, BMI, and WWI. Logistic regression and Pearson correlation analyses were applied to investigate the relationship between the above key variables.

Logistic regression results showed that CVD was a risk factor for NMSC (OR: 1.83, 95% CI: 1.01 ~ 3.34, p = 0.048); however, there was no statistically significant association between CVD subgroups and NMSC. In addition, SIRI, BMI, and WWI partially mediated the association between CVD and NMSC (p < .001), but SII did not alter the relationship (p > 0.05). Bootstrap test confirmed the stability of the results of the mediation analysis.

CVD increases the risk of developing NMSC, and obesity and inflammation partially mediate the relationship. Weight loss and control of inflammation may be beneficial in reducing the prevalence of CVD and NMSC.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), non-melanoma skin cancer (MONDO:0002656)

## Full-text entities

- **Genes:** GRN (granulin precursor) [NCBI Gene 2896] {aka CLN11, FTD2, GEP, GP88, PCDGF, PEPI}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SERPINA3 (serpin family A member 3) [NCBI Gene 12] {aka AACT, ACT, GIG24, GIG25}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}
- **Diseases:** chronic diseases (MESH:D002908), lung cancer (MESH:D008175), CHD (MESH:D003327), carcinogenesis (MESH:D063646), cancer (MESH:D009369), Weight loss (MESH:D015431), Obese (MESH:D009765), stroke (MESH:D020521), heart attack (MESH:D009203), NMSCs (MESH:D012878), metabolic disorders (MESH:D008659), non-melanoma (MESH:D008545), Angina (MESH:D000787), atherosclerosis (MESH:D050197), Diabetes (MESH:D003920), sebaceous gland carcinoma (MESH:D012626), SCCs (MESH:D002294), COVID-19 (MESH:D000086382), coronary artery disease (MESH:D003324), Inflammation (MESH:D007249), BCCs (MESH:D002280), Thrombosis (MESH:D013927), CHF (MESH:D006333), CVD (MESH:D002318), Hypertension (MESH:D006973), apocrine sweat gland adenocarcinoma (MESH:D013544), central obesity (MESH:D056128)
- **Chemicals:** Glucose (MESH:D005947), alcohol (MESH:D000438), Canakinumab (MESH:C541220)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13008061/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC13008061/full.md

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Source: https://tomesphere.com/paper/PMC13008061