Background: Recent advances in cancer diagnosis and treatment have significantly improved survival rates among women of reproductive age facing cancer. However, the potential iatrogenic loss of fertility caused by chemotherapeutic agents underscores the need to understand and predict chemotherapy-induced ovarian damage. This study addresses this gap by systematically reviewing the literature to investigate genetic markers associated with chemotherapy-induced ovarian failure (CIOF).Objective: The primary objective is to identify genetic markers linked to CIOF, contributing to a comprehensive understanding of the factors influencing fertility preservation in female cancer survivors.Methods: A systematic review was conducted using PubMed, EMBASE, Web of Science, Scopus, and OVID electronic databases from inception through December 2023. Studies were included if they featured genomic assessments of genes or polymorphisms related to CIOF in women with histologically confirmed tumors. Exclusion criteria comprised in vitro and animal studies, reviews, and pilot studies. The resulting four human-based studies were scrutinized for insights into genetic influences on CIOF.Results: Of the 5179 articles initially identified, four studies met the inclusion criteria, focusing on alkylating agents, particularly cyclophosphamide, and anthracyclines. Su et al. exploredCYP3A41Bvariants, revealing modified associations with CIOF based on age. Charo et al. investigatedGSTA1andCYP2C19polymorphisms, emphasizing the need to consider age and tamoxifen therapy in assessing associations. Oktay et al. delved into the impact of BRCA mutations on anti-Müllerian hormone (AMH) levels post-chemotherapy, supported by in vitro assays. Van der Perk et al. focused on childhood cancer survivors and revealed significant associations ofCYP3A43andCYP2B6*2SNPs with AMH levels.Conclusions: This systematic review analyzes evidence regarding genetic markers influencing CIOF, emphasizing the complex interplay of age, specific genetic variants, and chemotherapy regimens. The findings underscore the need for a personalized approach in assessing CIOF risk, integrating genetic markers with traditional ovarian reserve testing. The implications of this study extend to potential advancements in fertility preservation strategies, offering clinicians a comprehensive baseline assessment for tailored interventions based on each patient’s unique genetic profile. Further research is essential to validate these findings and establish a robust framework for integrating genetic markers into clinical practice.
背景：癌症诊断与治疗的最新进展显著提高了育龄期女性癌症患者的生存率。然而，化疗药物可能导致的医源性生育能力丧失，凸显了理解和预测化疗所致卵巢损伤的必要性。本研究通过系统综述文献，探讨与化疗诱导卵巢功能衰竭相关的遗传标记，以填补这一研究空白。 目的：主要目标是识别与化疗诱导卵巢功能衰竭相关的遗传标记，从而全面理解影响女性癌症幸存者生育力保存的因素。 方法：系统检索了自建库至2023年12月的PubMed、EMBASE、Web of Science、Scopus和OVID电子数据库。纳入标准为包含对经组织学确诊肿瘤的女性进行与化疗诱导卵巢功能衰竭相关的基因或多态性基因组评估的研究。排除标准包括体外研究、动物研究、综述和预试验研究。最终纳入的四项以人为对象的研究被仔细审查，以探究遗传因素对化疗诱导卵巢功能衰竭的影响。 结果：在最初识别的5179篇文章中，四项研究符合纳入标准，重点关注烷化剂（特别是环磷酰胺）和蒽环类药物。Su等人探讨了CYP3A4*1B变异，揭示了其与化疗诱导卵巢功能衰竭的关联随年龄而变化。Charo等人研究了GSTA1和CYP2C19多态性，强调在评估关联性时需考虑年龄和他莫昔芬治疗。Oktay等人深入研究了BRCA突变对化疗后抗苗勒管激素水平的影响，并得到体外实验支持。Van der Perk等人聚焦于儿童期癌症幸存者，揭示了CYP3A43和CYP2B6*2单核苷酸多态性与抗苗勒管激素水平的显著关联。 结论：本系统综述分析了关于影响化疗诱导卵巢功能衰竭的遗传标记的证据，强调了年龄、特定遗传变异和化疗方案之间复杂的相互作用。研究结果强调需要采用个性化方法来评估化疗诱导卵巢功能衰竭风险，将遗传标记与传统卵巢储备功能检测相结合。本研究的意义延伸至生育力保存策略的潜在进展，为临床医生提供了基于患者独特遗传特征进行个体化干预的全面基线评估。进一步的研究对于验证这些发现以及建立将遗传标记整合到临床实践中的稳健框架至关重要。
Molecular Factors Predicting Ovarian Chemotoxicity in Fertile Women: A Systematic Review
肿瘤(癌症)患者之家