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Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population
Authors:Gong-Hao He  Jun Lu  Pan-Pan Shi  Wei Xia  Sun-Jun Yin  Tian-Bo Jin  De-Dian Chen  Gui-Li Xu
Affiliation:1. Department of Pharmacy, Kunming General Hospital of Chengdu Military Region, Kunming 650032, China;2. Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Xi''an Jiaotong University, Xi''an 710061, China;3. National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi''an 710069, China;4. Department of Breast, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China
Abstract:Previous investigations indicated that histamine receptor H4 (HRH4) played important roles in many aspects of breast cancer pathogenesis, and that the polymorphisms of HRH4 gene may result in expression and functional changes of HRH4 proteins. However, the relationship between polymorphisms of HRH4 and breast cancer risk and malignant degree is unclear. In the present study, we conducted a case–control investigation among 185 Chinese Han breast cancer patients and 199 ethnicity-matched health controls. Four tag-SNPs (i.e. rs623590, rs16940762, rs11662595 and rs1421125) of HRH4 were genotyped and association analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. We found that the T allele of rs623590 had a decreased risk of breast cancer (adjusted OR, 0.667; 95% CI, 0.486–0.913; P = 0.012) while the A allele of rs1421125 had an increased risk (adjusted OR, 1.653; 95% CI, 1.139–2.397; P = 0.008). Further haplotype analysis showed that the CAA haplotype of rs623590–rs11662595–rs1421125 was more frequent among patients with breast cancer (adjusted OR, 1.856; 95% CI, 1.236–2.787; P = 0.003). Additionally, polymorphisms of rs623590 and rs11662595 were also correlated with clinical stages, lymph node involvement, and HER2 status. These findings indicated that the variants of rs623590, rs11662595 and rs1421125 genotypes of HRH4 gene were significantly associated with the risk and malignant degree of breast cancer in Chinese Han populations, which may provide us novel insight into the pathogenesis of breast cancer although further studies with larger participants worldwide are still needed for conclusion validation.
Keywords:BMI, body mass index   CI, confidence interval   DIC, ductal invasive carcinoma   HA, histamine   HRH4, histamine receptor H4   HWE, Hardy&ndash  Weinberg Equilibrium   LIC, lobular invasive carcinoma   ORs, odds ratios
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