Page 198 - EJMO-9-2

Eurasian Journal of Medicine

and Oncology

ORIGINAL RESEARCH ARTICLE
Causal association between Vitamin D levels

and head-and-neck cancer: A Mendelian
randomization study

1
2
Xiaosong Ru 1 , Ziying Su , and Yong Guo *
1 The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang,
China
2 Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical
University, Hangzhou, Zhejiang, China

Abstract

Observational studies have revealed inconsistent findings regarding the association
between Vitamin D levels and head-and-neck cancer (HNC). Therefore, this study
aimed to examine the possible causality of Vitamin D for HNC risk using two-sample
Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Single-
nucleotide polymorphisms closely associated with Vitamin D levels were selected
from the genome-wide association research database as instrumental variables. The
analytical approaches utilized included inverse variance weighted (IVW), MR-Egger,
weighted median, simple mode, and weighted mode. Sensitivity analysis was
performed to verify the robustness of MR findings. In addition, the causation of
Vitamin D on HNC risk was assessed by controlling for the influences of smoking and
*Corresponding author: alcohol intake through MVMR analysis. IVW (odds ratio = 0.9958, 95% confidence
Yong Guo interval = 0.9934 – 0.9983, p = 0.0007) indicated that Vitamin D levels were negatively
(guoyong1047@zcmu.edu.cn)
related to HNC risk. The weighted median yielded the same result. The results of
Citation: Ru X, Su Z, Guo Y. the MVMR analysis further supported the role of Vitamin D in mitigating HNC risk.
Causal association between
Vitamin D levels and head-and-neck The sensitivity analysis revealed the absence of heterogeneity or pleiotropy of the
cancer: A Mendelian randomization instrumental variables, proving our results reliable without significant bias. This study
study. Eurasian J Med Oncol. offers genetic evidence in favor of the causality of Vitamin D for HNC risk. Increasing
2025;9(2):190-198.
doi: 10.36922/ejmo.7099 Vitamin D intake may help lower HNC risk.
Received: December 7, 2024
Keywords: Head-and-neck cancer; Vitamin D; Mendelian randomization; Causality
Revised: January 23, 2025
Accepted: February 18, 2025
Published online: April 15, 2025 1. Introduction
Copyright: © 2025 Author(s).
This is an Open-Access article Head-and-neck cancer (HNC) is a general term for malignant tumors of multiple sites in
distributed under the terms of the the upper digestive and respiratory tracts, 90% of which have squamous cell carcinoma
Creative Commons Attribution
License, permitting distribution, pathology, including cancers of four anatomical sites: nasal cavity, oral cavity, pharynx,
1
and reproduction in any medium, and larynx. The main risk factors for HNC include smoking, alcohol consumption,
provided the original work is and human papillomavirus infections. According to the global cancer statistics
1,2
properly cited.
in 2020, HNC accounted for approximately 7.4% of the total cancer population, and
Publisher’s Note: AccScience HNC-related deaths accounted for 5.1% of all cancer-related deaths. Furthermore, the
3
Publishing remains neutral with 4
regard to jurisdictional claims in incidence of this type of cancer is steadily rising annually. In addition, the outcomes for
published maps and institutional people diagnosed with HNC is typically unfavorable, as evidenced by a 5-year overall
affiliations.
Volume 9 Issue 2 (2025) 190 doi: 10.36922/ejmo.7099