The association between non-melanoma skin cancer and a young dimorphic Alu element within the major histocompatibility complex class I genomic region
The association between non-melanoma skin cancer and a young dimorphic Alu element within the major histocompatibility complex class I genomic region
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DOI：
10.1111/j.1399-0039.2006.00631.x
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发表时间：
2006-08-01
期刊：
影响因子：
--
通讯作者：
Kulski, J. K.
中科院分区：
文献类型：
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作者：
Dunn, D. S.;Inok, H.;Kulski, J. K.
位于主要组织相容性复合体(MHC)I类区域的一个非黑色素瘤皮肤癌(NMSC)易感基因是利用高密度微卫星标记发现的人类白细胞抗原C基因的端粒。在这里，我们使用来自西澳大利亚Busselton镇的154名NMSC患者和213名正常对照的相同DNA样本，扩展了先前的微卫星研究，并研究了MHC I类区域内五个多态Alu插入(POALIN)之间的关系及其与NMSC的关联。根据Fisher‘s精确检验，位于NMSC易感区域端粒的AluyTf插入在NMSC患者中的基因型分布显著增加，在对照组中不符合Hardy-Weinberg平衡。MICB基因内含子I内的AluyMICB基因座和位于人类白细胞抗原-A、-G和-F基因簇基因组区域的其他3个POALIN(AluyHJ、AluyHG和AluyHF)在癌症患者和对照组之间无差异。10对POALIN基因座的显著连锁不平衡检验和两个POALIN基因座单倍型频率的估计也显示了病例组和对照组之间的AluyTf差异。综上所述，位于NMSC易感基因附近的MHC-I类POALIN AluyTf与NMSC密切相关。这一发现使用了五个不同的多态Alu插入标记，支持了先前的微卫星关联研究，即位于AluyTF插入附近的一个或多个基因在NMSC中具有潜在的作用。
A non-melanoma skin cancer (NMSC) susceptibility locus within the major histocompatibility complex (MHC) class I region was previously identified telomeric of the HLA-C gene using high-density microsatellite markers. Here, we have extended the previous microsatellite study by using the same DNA samples obtained from 154 NMSC patients and 213 normal controls from the town of Busselton in Western Australia and examined the relationship between five polymorphic Alu insertions (POALINs) within the MHC class I region and their association with NMSC. The genotype distribution of the AluyTF insertion that is located within the NMSC susceptibility region telomeric of the HLA-C gene was significantly increased according to the Fisher's exact test in the NMSC patients, and it was not in Hardy-Weinberg equilibrium in the control group. There was no difference between the cancer patients and controls for the genotypes of the AluyMICB locus within intron I of the MICB gene and the other three POALINs (AluyHJ, AluyHG and AluyHF) that are located within the genomic region of the HLA-A, -G and -F gene cluster. The test for significant linkage disequilibrium for 10 pairs of POALIN loci and estimations of two locus POALIN haplotype frequencies also revealed AluyTF differences between the cases and controls. In conclusion, the MHC class I POALIN, AluyTF, that is located within the NMSC susceptibility locus and near the HLA-C gene was strongly associated with NMSC. This finding, using five different polymorphic Alu insertion markers, supports the previous microsatellite association study that one or more genes located in close proximity to the AluyTF insertion has a potential role in NMSC.