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白细胞介素-10启动子多态性与非黑色素瘤皮肤癌的关系——非白种人皮肤癌患者的病例研究

Involvement of interleukin-10 promoter polymorphisms in nonmelanoma skin cancers-a case study in non-Caucasian skin cancer patients.

作者信息

Nagano Tohru, Kunisada Makoto, Yu Xijun, Masaki Taro, Nishigori Chikako

机构信息

Division of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan.

出版信息

Photochem Photobiol. 2008 Jan-Feb;84(1):63-6. doi: 10.1111/j.1751-1097.2007.00245.x.

Abstract

Interleukin 10 (IL-10) is a potent immunosuppressive cytokine, therefore elevated IL-10 expression has been implicated in inhibition of antitumor immune response. IL-10 gene promoter polymorphism has been shown to be involved in susceptibility to skin cancers, but there has been no report focusing on susceptibility to skin cancers among non-Caucasian populations. We enrolled 129 patients with skin cancers and 50 age- and sex-matched healthy controls between April 2004 and March 2007. Genomic DNA was extracted from patients' blood samples and IL-10 promoter polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism or direct sequencing. The distribution of the frequency of allele or haplotype of IL-10 gene promoter in Japanese was quite different from that of Europeans. No significant differences could be demonstrated in the frequency of allele or haplotype of IL-10 gene promoter between the patient group and the control group. However, the frequency of the low-IL-10 expression haplotype was significantly high in Bowen's disease subgroup. The frequency of low expression IL-10 promoter genotype was significantly less (P = 0.009, chi(2) = 6.74) in the group of nonmelanoma skin cancer generated on sun-exposed areas in comparison with that on covered areas. Our results indicated that low expression haplotype of IL-10 in Bowen's disease may inhibit the escape of tumor cells from immune surveillance, resulting in suppression of tumor growth and tumor invasion to the dermis. Moreover, high IL-10-expressing haplotype of IL-10 promoter may be a risk factor for photocarcinogenesis.

摘要

白细胞介素10(IL-10)是一种强效的免疫抑制细胞因子,因此IL-10表达升高与抗肿瘤免疫反应的抑制有关。IL-10基因启动子多态性已被证明与皮肤癌易感性有关,但尚无针对非白种人群皮肤癌易感性的报道。我们在2004年4月至2007年3月期间招募了129例皮肤癌患者和50例年龄及性别匹配的健康对照。从患者血液样本中提取基因组DNA,并使用聚合酶链反应-限制性片段长度多态性或直接测序法鉴定IL-启动子多态性。日本人中IL-10基因启动子等位基因或单倍型频率分布与欧洲人有很大不同。患者组和对照组之间IL-10基因启动子等位基因或单倍型频率无显著差异。然而,在鲍温病亚组中,低IL-10表达单倍型的频率显著较高。与遮盖部位相比,暴露部位产生的非黑色素瘤皮肤癌组中低表达IL-10启动子基因型的频率显著更低(P = 0.009,χ² = 6.74)。我们的结果表明,鲍温病中IL-10的低表达单倍型可能抑制肿瘤细胞从免疫监视中逃逸,从而抑制肿瘤生长和肿瘤向真皮层浸润。此外,IL-启动子的高IL-10表达单倍型可能是光致癌作用的一个危险因素。

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