BACKGROUND: Breast cancer is one of the leading causes of cancer-related deaths for women. Numerous studies have shown that single-nucleotide polymorphisms (SNPs) on the ESR1 gene are associated to this disease. However, data and conclusions are inconsistent and controversial.
MATERIAL AND METHODS: To investigate the association between PvuII (rs2234693), XbaI (rs9340799) and P325P (rs1801132) polymorphisms of ESR1 gene with the risk of breast cancer under different population categorizations, we searched multiple databases for data collection, and performed the meta-analysis on a total of 25 case-control studies. Three different comparison models – dominant model, recessive model, and homozygote comparison model – were applied to evaluate the association.
RESULTS: Our results indicated that people with TT+TC or TT genotype were at a greater risk of developing breast cancer than those with CC genotype in the PvuII polymorphism. While for XbaI and P325P polymorphisms, no significance was found using any of the 3 models. Furthermore, the data were also stratified into different subgroups according to the ethnicity (white or Asian) and source of controls (hospital-based or population-based), and separate analyses were conducted to assess the association. The ethnicity subgroup assessment showed that the higher risk of breast cancer for TT genotype of PvuII polymorphism than CC genotype only occurred in Asian people, but not in white populations. For the source-stratified subgroup analysis, significant association suggested that people with TT + TC genotype were at a greater risk of developing breast cancer than those with CC genotype in the hospital-based subgroup.
CONCLUSIONS: Thus, this meta-analysis clarified the inconsistent conclusions from previous studies, conducted analyses for the entire population as well as for different subgroups using diverse population categorization strategies, and has the potential to help provide a personalized risk estimate for breast cancer susceptibility.

Keywords: Breast Neoplasms - genetics, Case-Control Studies, Estrogen Receptor Modulators - metabolism, Estrogen Receptor alpha - genetics, Female, Genes, Dominant, Genes, Recessive, Genetic Predisposition to Disease, Genotype, Homozygote, Hospitalization, Humans, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Risk Factors