Nagano Tohru, Kunisada Makoto, Yu Xijun, Masaki Taro, Nishigori Chikako
Division of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan.
Photochem Photobiol. 2008 Jan-Feb;84(1):63-6. doi: 10.1111/j.1751-1097.2007.00245.x.
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.
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。