Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in Caucasian women
Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in Caucasian women
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DOI：
10.1158/1078-0432.ccr-05-0001
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发表时间：
2005-08-15
影响因子：
11.5
通讯作者：
Zeillinger, R
中科院分区：
文献类型：
--
作者：
Hefler, LA;Grimm, C;Zeillinger, R
目的：已知精氨酸编码基因的遗传多态性易患恶性疾病。白细胞介素（IL）-1和IL-6在乳腺癌的发生中起着重要作用。编码IL-1（IL 1）和IL-6（IL 6）的基因多态性是否也影响乳腺癌风险尚不清楚。在本病例对照研究中，我们确定了IL 1基因簇的三个多态性[IL 1 α基因（IL 1A）的-889 C/T多态性，IL 1 β启动子的-511 C/T多态性，（IL 1B启动子），IL 1 β外显子5的多态性（IL 1B外显子5）]，IL 1受体拮抗剂基因（IL 1 RN）内含子2中的86-bp重复序列，采用PCR和焦磷酸测序技术检测了269例乳腺癌患者和227例健康对照者IL 6基因-174 G/C多态性。V基因簇内的多态性和相应的单倍型与乳腺癌的存在和表型无关。IL 6基因多态性与乳腺癌的发生有显著相关性。携带一个或两个高风险等位基因的女性与低风险等位基因纯合子女性的比值比分别为1.5（95%置信区间，1.04-2.3; P=0.04）和2.0（95%置信区间，1.1-3.6; P=0.02）。IL 6多态性和各种临床病理变量之间没有关联被确定。结论：虽然IL 1基因簇内的多态性似乎不影响乳腺癌的风险或表型，-174C IL 6等位基因的存在增加了高加索妇女乳腺癌的风险，呈剂量依赖性。
Purpose: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown.Experimental Design: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1 alpha gene (IL1A), -511 C/T polymorphism of the IL1 beta promoter (IL1B promoter), a polymorphism of IL1 beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing.Results: Polymorphisms within the V gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P=0.04) and 2.0 (95% confidence interval, 1.1-3.6; P=0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables.Conclusions: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.