Genetic variations, including single nucleotide polymorphism, were closely related to the occurrence of breast cancer. Genome-wide association studies (GWAS) have detected many SNPs were related to breast cancer susceptibility in tumor-related genes such as PD-1, FGFR2, ESR1, PTEN, and MAP3K1 [17–19]. The effect of IL-7R SNPs on breast cancer susceptibility in Chinese Han population is not clear at present. In this present work, we revealed that the allele and genotype frequency distribution of IL-7R SNPs (rs969129, rs10213865 and rs6451231) was significantly different between the case and control groups, and they increased the risk of breast cancer. In the age stratified analysis subgroup, IL-7R-rs6451231 significantly increased breast cancer risk among those older than 50 years. Rs10213865, rs969129 and rs6451231 were also significantly correlated with some clinical parameters, such as tumor size, ER status and Ki67 stress status. We have also observed that haplotype CGAG increases breast cancer susceptibility. These results provided some support for the impact of genetic variation of IL-7R on breast cancer risk among Chinese Han population.
IL-7R, located on chromosome 5p13, is a heterodimer consisting of two strands (IL-7Rα and common γ chain). The binding of IL-7R and IL-7 leads to the activation of tumor-related signaling pathways, including PEDF Induced Signaling and Interleukin-7 signaling pathway, etc [20, 21]. At present, there are many studies on the relevant mechanism of IL-7R in lung cancer. Researchs have reported that IL-7/IL-7R can affect the production level of vascular endothelial growth factor in lung cancer and the formation of lymphatic vessels through the c-fos/c-jun pathway . It can also affect the production of cyclin D1 by activating the AP1 pathway, thus accelerating the proliferation of breast cancer cells . However, there are few researchs has been done on the mechanism of IL-7R in breast cancer. Only studies reported the expression levels of IL-7 and IL-7R have been observed to increase significantly in breast cancer [8, 11], and IL-7 can affect the proliferation rate of breast cancer cells . Therefore, further studies on the mechanism of IL-7R and breast cancer are still needed.
Genetic variation polymorphisms of IL-7R has been reported to affect the occurrence of many diseases. Sinha et al.  found that polymorphisms of IL-7R (rs1494555 and rs6897932) were associated with asthma in the northern Indian population. IL-7R -rs6897932 (C/T) was related to the susceptibility of systemic lupus erythematosu . In our study, we explored the influence of IL-7R SNPs (rs6451231, rs10213865, rs118137916, rs969129, and rs10053847) on breast cancer susceptibility in Chinese Han population. Bai et al.  that IL-7R SNPs (rs6451231 and rs969129) were significantly correlated with an increased rheumatoid arthritis (RA) susceptibility under multiple genetic model, and the haplotype GAGC constructed by IL-7R SNPs (rs118137916, rs969129, rs6451231 and rs10053847) also increased the RA risk.
Zhang et al.  explored the effect of IL-7R polymorphism on lung cancer risk. The rs10053847 and rs10213865 variant was observed to be correlated with a decreased breast cancer risk under multiple genetic model, and AGAA haplotypes (rs10213865, rs969129, rs118137916, and rs10053847) also increased breast cancer risk. However, our study observed that IL-7R SNPs (rs969129, rs10213865 and rs6451231) were significantly increased breast cancer risk, and haplotype CGAG (rs10213865, rs118137916, rs969129 and rs10053847) significantly increased breast cancer susceptibility. As far as we know, our study is the first to explore the relationship between IL-7R polymorphism and susceptibility to breast cancer.
There are some limitations to this study that cannot be ignored. First, this was a hospital-based case-control study involving only Han women, and the applicability of our conclusions should be explored in other ethnic populations. Second, our sample size was relatively small, and false negative results cannot be excluded. Despite the above limitations, the results of this study provide a scientific basis for future research on IL-7R gene and breast cancer.
In conclusion, our study was the first to found that IL-7R SNPs (rs6451231, rs10213865 and rs969129) were significantly increased breast cancer risk, which provides a basis for further mechanism research of IL-7R and breast cancer.