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Background:  Human epidermal growth factor receptor 2 (HER2) plays an important role in the development and progression of breast cancer. To understand the precise association, this meta-analysis was conducted to estimate the association between HER2 Ile655Val  single nucleotide polymorphism (SNP) and susceptibility to early-onset breast cancer.Methods:  A comprehensive database retrieval from PubMed, Embase, Web of Science and Google Scholar was pooled to investigate links between the HER2 Ile655Val  SNP and risk of breast cancer. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to appraise the association under the additive model (Ile vs. Val), dominant model (Val/Val + Ile/Val vs. Ile/Ile), and recessive model (Val/Val vs. Ile/Val + Ile/Ile).Results:  Seventeen relevant studies with 11,749 cases and 8,105 controls were finally included. We found that HER2 Ile655Val  SNP is associated with an increased risk of breast cancer in an additive and dominant model. In the subgroup analysis with age stratification, a significant association between the HER2 codon 655 SNP and the risk of breast cancer was found in young women in an additive, dominant, and recessive model; conversely, no significant associations were indicated in older women. In the breast cancer subgroup, HER2 Ile655Val  SNP was significantly associated with younger age women with breast cancer in the dominant model. In contrast, no association between the HER2 codon 655 SNP and age was found in control populations.Conclusion:  Our findings suggest that the Val allele in HER2 codon 655 SNP is strongly associated with breast cancer susceptibility in the young female population and is also significantly associated with younger age in women with breast cancer. HER2 Ile655Val  SNP might be a susceptibility factor that favours early-onset breast cancer.

HER2Ile655Val Single Nucleotide Polymorphism Associated with Early-Onset Breast Cancer Susceptibility: A Systematic Review and Meta-Analysis