Causal role of immune cells on cervical cancer onset revealed by two-sample Mendelian randomization study

Sep 21, 2026

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Study aims to determine causal effects of immune traits on cervical cancer onset and on non-neoplastic cervical conditions. GWAS data for 731 immunophenotypes and separate six GWAS datasets for cervical cancer from FinnGen were analyzed using two-sample Mendelian randomization with MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Results suggest immune traits may causally relate to multiple cervix inflammatory and noninflammatory disorders, carcinoma in situ, adenocarcinomas, squamous cell neoplasms, and cervical carcinoma, and highlight classic monocytes’ strong associations. Findings also indicate BAFF-R+ B cells can impede malignant cervical cancer progression, supporting immune-informed clinical research.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Background on cervical cancer and treatment considerations

Immune response, tumor microenvironment, and HPV involvement

Mendelian randomization overview and key assumptions

Methods and analysis approach

GWAS sources and immunophenotype data

Two-sample MR models used

Results and key findings

Causal links across inflammatory and noninflammatory cervix conditions

Associations involving monocytes and BAFF-R+ B cells

Conclusion

Summary of causal evidence and research implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Causal role of immune cells on cervical cancer onset revealed by two‑sample Mendelian randomization study Zicheng Zhao1,4, Pengxian Yan1,4, Xiaoyu Zhang1,2, Xiaomin Yu1, Fengchun Lv 1, Mingyu Gong1 & Xiu‑AnYang1,3* Cervical cancer (CC) is a prevalent gynecological cancer worldwide that significantly impacts the quality of life and the physical and mental well‑being of women. However, there have been limited studies utilizing Mendelian randomization (MR) analysis to investigate the connection between immune cells and CC. This study is to investigate the causal effects of immune traits on CC and non‑ neoplastic conditions of the cervix. The GWAS data for 731 immunophenotypes and six GWAS data for CC from the FinnGen database were downloaded. Subsequently, a two‑sample MR analysis was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode methods. Our study has identified the potential causal effects of immune traits on inflammatory diseases of the cervix, other noninflammatory disorders ofthe cervix uteri, carcinoma in situ of cervix uteri, adenocarcinomas of cervix, squamous cell neoplasms and carcinoma of cervix, as well as malignant neoplasm of the cervix uteri, with the respective numbers being 8, 6, 11, 8, 23, and 12, respectively. A strong correlation between classic monocytes and various cervical diseases was revealed. Furthermore, we discovered that B cells expressing BAFF‑R have the ability to impede the advancement of malignant CC, specifically squamous cell neoplasms and carcinoma of cervix. Our study has demonstrated a significant association between immune traits and both CC and non‑ neoplastic conditions of the cervix through two‑sample Mendelian randomization, providing valuable insights for future clinical research. Keywords Cervical cancer, Cervical non-neoplastic conditions, Immune traits, Two-sample Mendelian randomization analysis, Causal effects Cervical cancer (CC) is widely recognized as a significant public health issue and holds the position of being the fourth deadliest form of cancer among women across the globe1,2. According to WHO data, approximately 604,000 new cases were diagnosed globally in 20203. CC, especially in developing countries, is identified as the primary cause of death for women worldwide, as stated by the International Agency for Research on Cancer2. While most women with early-stage tumors can receive treatment, many experience long-term complications. Chemoradiation (CAT) is the recommended treatment for locally advanced CC4,5. The timing of CAT plays a crucial role in determining survival outcomes, and its efficacy in underdeveloped nations remains uncertain due to the absence of suitable screening techniques6,7. Numerous factors, such as smoking, a compromised immune system, and prolonged use of oral contraceptives, contribute to the development of CC8. The primary cause ofCC is a persistent infection with high-risk types of the human papillomavirus (HPV), particularly HPV16 and/or HPV18, which are the most common culprits9. Therefore, further exploration of these HPV types may uncover causes that are linked either directly or indirectly to other malignancies in the human reproductive system. It is well-documented that the tumor microenvironment (TME) plays crucial roles in the occurrence and progression of tumors. In the case ofCC, both innate and acquired immune responses are present in HPV-infected lesions10. For instance, cell migration to the squamous 1Laboratory of Genetic Engineering and Genomics, School of Basic Medical Sciences, Chengde Medical University, Chengde 067000, Hebei, China. 2Graduate School of Chengde Medical University, Chengde 067000, China. 3Hebei Key Laboratory of Nerve Injury and Repair, Chengde Medical University, Chengde 067000, China. 4These authors contributed equally: Zicheng Zhao and Pengxian Yan.*[email

FAQs

What was the main goal of this two-sample Mendelian randomization study?

To evaluate causal effects of immune traits on cervical cancer onset and on non-neoplastic cervical conditions using genetic instruments from GWAS data.

Which Mendelian randomization methods were applied in the analysis?

The study used MR Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode.

What immune cell findings were reported as strongly linked to cervical diseases?

Classic monocytes showed strong correlations with various cervical diseases, and BAFF-R expressing B cells were found to impede the advancement of malignant cervical cancer, particularly squamous cell neoplasms and cervical carcinoma.

Sep 21, 2026

Uploaded by Aria