Association between ESR1 polymorphisms (XbaI & PvuII) and breast cancer risk: a comprehensive meta-analysis of case-control studies.

Background: 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.

Aim: 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.

Methods: 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 I² and Cochran's Q tests, while Egger's and Begg's tests assessed publication bias. Sensitivity analyses tested the robustness of results.

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.