Original Investigation

Blood Manganese and Risk of Squamous Cell Carcinomas of the Head and Neck

JAMA Otolaryngology–Head & Neck Surgery 10.1001/jamaoto.2026.1749

July 02, 2026 at 11:00 AM EDT

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Are variations in the genetically predicted whole blood concentration of manganese associated with risk of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas (SCCs)?In this 2-sample -mendelian randomization study using a genetic instrument for blood manganese, with requisite data derived from a meta-analysis of 3 individual-level genome-wide association study datasets from 6564 Scandinavian participants, increases in the genetically predicted whole blood concentration of manganese were associated with increased risk of oral cavity SCC and human papillomavirus–positive oropharyngeal SCC.Increases in blood manganese levels were found to be associated with increased risk of multiple head and neck cancers, and further investigation into this association is warranted to inform public health strategies to mitigate these risks.

Corresponding Author: Benjamin Clay, MBBChir, Department of Surgery, East Suffolk and North Essex NHS Foundation Trust, Ipswich IP4 5PD, United Kingdom (bjc61@cam.ac.uk).

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