Association between XRCC3 p.Thr241Met polymorphism and risk of glioma: A systematic review and meta-analysis

Shing Cheng Tan; Teck Yew Low; Hafiz Muhammad Jafar Hussain; Mohamad Ayub Khan Sharzehan; Hilary Sito; Hamed Kord-Varkaneh; Md Asiful Islam

doi:10.1371/journal.pone.0276313

Association between XRCC3 p.Thr241Met polymorphism and risk of glioma: A systematic review and meta-analysis

PLoS One. 2022 Oct 20;17(10):e0276313. doi: 10.1371/journal.pone.0276313. eCollection 2022.

Authors

Shing Cheng Tan¹, Teck Yew Low¹, Hafiz Muhammad Jafar Hussain², Mohamad Ayub Khan Sharzehan¹, Hilary Sito¹, Hamed Kord-Varkaneh³, Md Asiful Islam⁴

Affiliations

¹ UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States of America.
³ Department of Clinical Nutrition and Dietetics, Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.

Abstract

Background: The XRCC3 p.Thr241Met (rs861539) polymorphism has been extensively studied for its association with glioma risk, but results remain conflicting. Therefore, we performed a systematic review and meta-analysis to resolve this inconsistency.

Methods: Studies published up to June 10, 2022, were searched in PubMed, Web of Science, Scopus, VIP, Wanfang, and China National Knowledge Infrastructure databases and screened for eligibility. Then, the combined odds ratio (OR) of the included studies was estimated based on five genetic models, i.e., homozygous (Met/Met vs. Thr/Thr), heterozygous (Thr/Met vs. Thr/Thr), dominant (Thr/Met + Met/Met vs. Thr/Thr), recessive (Met/Met vs. Thr/Thr + Thr/Met) and allele (Met vs. Thr). The study protocol was preregistered at PROSPERO (registration number: CRD42021235704).

Results: Overall, our meta-analysis of 14 eligible studies involving 12,905 subjects showed that the p.Thr241Met polymorphism was significantly associated with increased glioma risk in both homozygous and recessive models (homozygous, OR = 1.381, 95% CI = 1.081-1.764, P = 0.010; recessive, OR = 1.305, 95% CI = 1.140-1.493, P<0.001). Subgroup analyses by ethnicity also revealed a statistically significant association under the two aforementioned genetic models, but only in the Asian population and not in Caucasians (P>0.05).

Conclusion: We demonstrated that the XRCC3 p.Thr241Met polymorphism is associated with an increased risk of glioma only in the homozygous and recessive models.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Case-Control Studies
Genetic Predisposition to Disease*
Glioma* / genetics
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Risk Factors

Substances

X-ray repair cross complementing protein 3

Grants and funding

Research in SCT’s laboratory is supported by the Research University Grant of Universiti Kebangsaan Malaysia (No. GUP-2020-076), the Fundamental Research Grant Scheme of the Ministry of Higher Education, Malaysia (No. FRGS/1/2019/SKK08/UKM/02/9), and the Higher Institution Center of Excellence (HICoE) grant of the Ministry of Higher Education, Malaysia (No. AKU49). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.