Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population
Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population
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人组胺受体H4基因多态性与中国汉族乳腺癌的相关性
DOI：
10.1016/j.gene.2013.02.020
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发表时间：
2013-05-01
期刊：
影响因子：
3.5
通讯作者：
Xu, Gui-Li
中科院分区：
文献类型：
--
作者：
He, Gong-Hao;Lu, Jun;Xu, Gui-Li
研究表明，组胺受体H4（histamine receptor H4，HRH 4）在乳腺癌的发病机制中起重要作用，HRH 4基因多态性可能导致HRH 4蛋白表达和功能的改变。但HRH 4基因多态性与乳腺癌发病风险及恶性程度的关系尚不清楚。本研究对185例汉族乳腺癌患者和199例健康对照者进行了病例对照研究。对HRH 4的4个tag-SNPs（rs623590、rs 16940762、rs 11662595和rs 1421125）进行基因分型和关联分析。比值比（OR）和95%置信区间（CI）用于评估相关性。我们发现rs623590的T等位基因降低了乳腺癌的风险（校正OR，0.667; 95%CI，0.486-0.913; P = 0.012），而rs 1421125的A等位基因增加了乳腺癌的风险（校正OR，1.653; 95%CI，1.139-2.397; P = 0.008）。进一步的单倍型分析显示CAA单倍型rs623590-rs 11662595-rs 1421125在乳腺癌患者中更常见（校正OR，1.856; 95%CI，1.236-2.787; P = 0.003）。此外，rs623590和rs 11662595的多态性也与临床分期、淋巴结受累和HERZ状态相关。这些结果表明，HRH 4基因rs623590、rs 11662595和rs 1421125基因型与中国汉族人群乳腺癌的发病风险和恶性程度显著相关，这可能为乳腺癌的发病机制提供新的见解，但结论的验证仍需在全球范围内进行更大规模的研究。(C)2013爱思唯尔有限公司版权所有。
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 HERZ 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. (C) 2013 Elsevier B.V. All rights reserved.