title: Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population.
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.
authors.affiliation: Department of Pharmacy, Kunming General Hospital of Chengdu Military Region, Kunming 650032, China.
authors.forename: Gong-Hao
authors.initials: GH
authors.lastname: He
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Sun-Jun
authors.initials: SJ
authors.lastname: Yin
authors.forename: Tian-Bo
authors.initials: TB
authors.lastname: Jin
authors.forename: De-Dian
authors.initials: DD
authors.lastname: Chen
authors.forename: Gui-Li
authors.initials: GL
authors.lastname: Xu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D011968:Receptors, Histamine / Q000235:genetics* / Q000378:metabolism; D000074040:Receptors, Histamine H4; D012307:Risk Factors
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C418607:HRH4 protein, human; C508053:ERBB2 protein, human