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