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Plasma protein LEG1 homolog and post-menopausal breast cancer risk in the UK Biobank

Platz, E. A.; Wang, Z.; Norton, E. L.; Syleouni, M.-E.; Gunter, M. J.; Guevara, M.; Riboli, E.; Mahamat Saleh, Y.; Smith-Byrne, K.; Burk, V. A.; Rohrmann, S.; Chatterjee, N.

2025-10-28 epidemiology
10.1101/2025.10.26.25338822 medRxiv
Show abstract

We previously identified and confirmed a positive association between plasma protein LEG1 homolog and incident post-menopausal breast cancer risk in two prospective cohort studies that measured the protein using the SomaScan platform. To further confirm this finding in a cohort that used a different proteomics platform, Olink, we investigated this association in the UK Biobank. Among 9,537 post-menopausal, White women followed for a median of 11 years and with protein data, 295 breast cancer cases were identified. Adjusting for breast cancer risk factors, per doubling, the hazard ratio was 1.14 (95% confidence interval CI 0.96-1.35). While the direction of association was consistent, the magnitude was not as strong as in our prior two cohorts (HR per doubling: 1.45, 1.24) and not statistically significant. Data from the UK Biobank provide modest support for plasma protein LEG1 homolog as a risk factor for post-menopausal breast cancer. A quantitative targeted assay is needed.

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