Behlam Ishan, Sudershan Amrit, Priya Indu, Sudershan Srishty, Saini Adesh K, Sharma Ravi, Younis Mohd, Sabharwal Rachna, Kumar Pawan, Manhas Sunita, Kumar Parvinder
Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Science & Research, Mullana, Ambala, Haryana, India.
Institute of Human Genetics, University of Jammu, Jammu, Jammu & Kashmir, India.
Breast Cancer Res Treat. 2025 Aug 8. doi: 10.1007/s10549-025-07800-9.
Breast cancer is one of the most common malignancies worldwide with notable geographic variation in incidence and mortality. Its risk is shaped by both environmental and genetic factors. Among the genetic contributors, ESR1 intronic polymorphisms such as XbaI and PvuII have been associated with breast cancer susceptibility, though results across populations remain inconsistent.
In light of these discrepancies, the present study aimed to comprehensively evaluate the association between ESR1 polymorphisms (XbaI and PvuII) and breast cancer risk using a meta-analytical approach, with particular attention to ethnicity-based subgroup effects and methodological rigor.
A systematic review was conducted per PRISMA guidelines using PubMed, Semantic Scholar, and Google Scholar. Twenty-six studies on XbaI and 28 on PvuII polymorphisms were included based on set criteria. Genotype and allele data were extracted, with study quality checked via the Newcastle-Ottawa Scale. Studies deviating from Hardy-Weinberg Equilibrium were excluded. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated across multiple genetic models. Heterogeneity was evaluated using I and Cochran's Q tests, while Egger's and Begg's tests assessed publication bias. Sensitivity analyses tested the robustness of results.
Meta-analysis of ESR1 XbaI showed no significant association with breast cancer risk across all genetic models (e.g., allelic OR = 0.9957; p = 0.898), including ethnic subgroups (African, Asian, Caucasian). Moderate heterogeneity was noted, but sensitivity and publication bias analyses confirmed result stability. Similarly, ESR1 PvuII showed no overall association (e.g., allelic OR = 0.9755; p = 0.406); however, significant associations emerged in Africans (e.g., dominant OR = 1.7992; p = 0.012), suggesting ethnic-specific susceptibility.
DISCUSSION & CONCLUSION: While ESR1 XbaI and PvuII polymorphisms are not associated with overall breast cancer risk, the PvuII variant may influence susceptibility in African populations. These findings highlight the need for large, multi-ethnic studies with standardized methods to clarify population-specific genetic risks.
乳腺癌是全球最常见的恶性肿瘤之一，其发病率和死亡率存在显著的地理差异。其风险受环境和遗传因素共同影响。在遗传因素中，ESR1基因内含子多态性如XbaI和PvuII与乳腺癌易感性相关，不过不同人群的研究结果并不一致。
鉴于这些差异，本研究旨在采用荟萃分析方法全面评估ESR1基因多态性（XbaI和PvuII）与乳腺癌风险之间的关联，特别关注基于种族的亚组效应和方法的严谨性。
按照PRISMA指南，使用PubMed、Semantic Scholar和谷歌学术进行系统综述。根据既定标准纳入了26项关于XbaI多态性的研究和28项关于PvuII多态性的研究。提取基因型和等位基因数据，并通过纽卡斯尔-渥太华量表检查研究质量。排除偏离哈迪-温伯格平衡的研究。在多个遗传模型中计算合并比值比（OR）及95%置信区间（CI）。使用I²和Cochran's Q检验评估异质性，同时用Egger's和Begg's检验评估发表偏倚。敏感性分析检验结果的稳健性。
ESR1基因XbaI多态性的荟萃分析显示，在所有遗传模型中，包括种族亚组（非洲人、亚洲人、高加索人），其与乳腺癌风险均无显著关联（例如，等位基因OR = 0.9957；p = 0.898）。观察到中度异质性，但敏感性和发表偏倚分析证实了结果的稳定性。同样，ESR1基因PvuII多态性总体上也无关联（例如，等位基因OR = 0.9755；p = 0.406）；然而，在非洲人群中出现了显著关联（例如，显性模型OR = 1.7992；p = 0.012），表明存在种族特异性易感性。
虽然ESR1基因XbaI和PvuII多态性与总体乳腺癌风险无关，但PvuII变异可能影响非洲人群的易感性。这些发现凸显了开展大规模、多民族且方法标准化的研究以明确特定人群遗传风险的必要性。
