SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1461015
Association Between ERCC2 Lys751Gln, Asp312Asn, and Arg156Arg Polymorphisms and Gynecological Cancer Susceptibility: A Meta-Analysis
Provisionally accepted
- Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
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Background ： Cervical, endometrial, and ovarian cancers are the most common gynecologic tumors. Excision repair cross-complementation group 2 (ERCC2) plays a critical role in nucleotide excision repair. ERCC2 polymorphisms can influence DNA damage repair mechanisms, potentially increasing tumors susceptibility. Therefore, we performed this meta-analysis to estimate these associations more precisely. Object：We summarized a larger sample for meta-analysis to explored the relationship between the ERCC2 Lys751Gln, Asp312Asn, and Arg156Arg and gynecological tumors. Methods ： We conducted a systematic search in PubMed, the Cochrane Library, Embase, and the Web of Science databases, covering studies up to October 2024. The odds ratio (OR) and 95% confidence interval (CI) were calculated using Stata 17 software. Results： Finally, a total of 19 studies (3,742 cases and 5,555 controls) were included for the ERCC2 Lys751Gln polymorphism. Additionally, 9 studies ( 2,170 cases and 3,582 controls ) were available for the Asp312Asn polymorphism, while 8 studies (3,521 cases and 3,971 controls)were included for the Arg156Arg . Of these, 16 focused on ovarian cancer , 8 on cervical cancer, and 10 on endometrial cancer. The ERCC2 Lys751Gln polymorphism was found to increase the risk of gynecologic neoplasms(C vs A：OR 1.33，95% CI 1.06-1.66；CC+CA vs AA：OR 1.33， 95% CI 1.11-1.59). Subgroup analysis by cancer type indicated an association of the Lys751Gln polymorphism with ovarian cancer (CC+CA vs AA：OR 1.39，95% CI 1.04-1.86), while no significant correlation was observed with cervical and endometrial cancers. Further subgroup analyses revealed that the Lys751Gln polymorphism increased the risk of gynecologic neoplasms in Caucasian and African populations, as well as in hospital-based studies. In contrast, the ERCC2 Asp312Asn polymorphism did not elevate the risk of gynecologic neoplasms, and the recessive gene variant was even protective against cervical cancer (CC+CA vs AA：OR 1.39，95% CI 1.04-1.86). Additionally, this study did not find an association between the Arg156Arg polymorphism and gynecologic tumor susceptibility. Conclusion：The ERCC2 Lys751Gln polymorphism is associated with an increased risk of gynecological tumors, particularly ovarian cancer. However, the Asp312Asn and Arg156Arg polymorphisms do not appear to elevate gynecological tumors susceptibility. Even the recessive gene model of Asp312Asn polymorphism may have a protective effect on cervical cancer.
Keywords: Gynecological neoplasms, ovarian cancer, cervical cancer, endometrial cancer, polymorphism, Meta-analysis
Received: 07 Jul 2024; Accepted: 12 Jun 2025.
Copyright: © 2025 Chen, Wang and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fen Chen, Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Chun-Guang Wang, Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
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