Association Analysis of IL-17A and IL-17F Polymorphisms in Chinese Han Women with Breast Cancer

Lihong Wang,Zhihua Wang,Da Pang,Baoling Tian,Wei Jiang,Sunhui Huang,Youxue Zhang,Yongdong Jiang,Yuwen Wang,Yue Yang

doi:10.1371/journal.pone.0034400

Abstract

BackgroundResearch into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women.Methodology and Principal FindingsWe genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P = 0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype Ars2275913Grs3819025Grs3748067, located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471 after correction for multiple testing).Conclusions and SignificanceOur results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.

Highlights

Breast cancer is the most common malignancy in women worldwide and its rate is increasing in both developed and developing countries [1]
Our results suggested that single-nucleotide polymorphisms (SNPs) in IL-17A but not IL-17F were associated with the risk of breast cancer
Polymorphisms in breast cancer patients and healthy controls are shown in Table 1 and Table 2

Summary

Introduction

Breast cancer is the most common malignancy in women worldwide and its rate is increasing in both developed and developing countries [1]. The etiology of breast cancer is complicated and not completely understood, but recent studies have focused on the roles of immunity and inflammation [2]. Th17 cells are generally important mediators of inflammation [3], autoimmune diseases [4] and cancer [5,6], through the production of IL-17A and IL-17F. Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women

Methods

Results

Discussion

Conclusion