The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population

We aimed to replicate a GWAS identified risk SNP rs17356907 in a Chinese population and examine the interaction of NTN4 and miR-17-92 on the susceptibility of breast cancer (BC). A case-control study was performed and SNPs genotyping was done using a TaqMan assay. The rs17356907 GG genotype and the rs17356907AG/GGrs982873CT/CC genotypes were associated with a decreased risk of BC. The NTN4 rs17356907 and miR-1792 (ie., rs9588884, rs982873, and rs1813389) had an interaction effect on BC susceptibility. Furthermore, the rs17356907GG genotype displayed higher levels of NTN4 mRNA. The NTN4 rs17356907 GG genotype may protect against the occurrence of BC by increasing the levels of NTN4 mRNA and NTN4/miR-17-92 polymorphisms have an interaction effect on BC risk. Introduction: Genome-wide association studies have identified a genetic variant rs17356907 in netrin 4 ( NTN4 ) as a risk locus of breast cancer (BC) in Europeans. NTN4 is a target gene of miR-17???92 cluster that is an oncogenic miRNA in BC development. We aimed to replicate the rs17356907 in a Chinese population and examine the interaction of NTN4 and miR-17???92 on BC susceptibility. Materials and methods: The rs17356907 in NTN4 and 3 additional polymorphisms in the promoter of miR-17???92 (ie, rs9588884, rs982873, and rs1813389) were determined in 415 patients with BC and 420 healthy controls using a TaqMan assay. The expression levels of NTN4 in BC and normal tissues were performed using the quantitative reverse transcription-PCR. Results: With reference to the rs17356907AA genotype, the GG genotype was associated with a decreased risk of BC with an adjusted OR of 0.38 (95% CI: 0.20-0.74). With reference to the rs17356907AA-rs982873CT/CC genotypes, the rs17356907 AG/GG-rs982873CT/CC genotypes were associated with a borderline decreased risk of BC with an adjusted OR of 0.67 (95% CI: 0.48-0.93). Gene-gene interaction analysis showed that the rs17356907-rs982873-rs9588884-rs1813389 was the best model on BC susceptibility. Furthermore, the rs17356907GG genotype displayed higher levels of NTN4 mRNA. Conclusions: The NTN4 rs17356907 may have a single and interactive effect with miR-17???92 polymorphisms on the risk of BC.

Automated summary

The study aimed to replicate a risk SNP rs17356907 in a Chinese population and investigate the interaction of NTN4 and miR-17-92 on breast cancer susceptibility. Results showed that the NTN4 rs17356907 GG genotype may protect against breast cancer by increasing NTN4 mRNA levels.