MHC Class II alleles in ulcerative colitis-associated colorectal cancer
MHC Class II alleles in ulcerative colitis-associated colorectal cancer
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DOI：
10.1136/gut.2008.166686
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发表时间：
2009-09-01
期刊：
影响因子：
24.5
通讯作者：
Smyrk, T. C.
中科院分区：
文献类型：
--
作者：
Garrity-Park, M. M.;Loftus, E. V., Jr.;Smyrk, T. C.
目的：溃疡性结肠炎患者是结直肠癌的高危人群。虽然先前的研究表明人类白细胞抗原基因与溃疡性结肠炎(UC)的易感性有关，但还没有人研究过人类白细胞抗原基因与UC-CRC之间的关系。因此，我们研究了UC-CRC患者和UC对照人群中的人类白细胞抗原-DR/DQ等位基因。此外，由于第二类反式激活因子(CIITA)基因的甲基化可能使肿瘤中的人类白细胞抗原表达沉默，因此我们将人类白细胞抗原等位基因频率与第二类反式激活因子基因甲基化和人类白细胞抗原-DR的表达相关联。方法：病例组和对照组在溃疡性结肠炎的病程/程度、年龄、种族和性别方面匹配，但与原发性硬化性胆管炎(PSC)无关。从114例UC-CRC患者和114例UC对照的存档组织块中提取DNA。采用序列特异性寡核苷酸聚合酶链式反应(SSO-PCR)进行HL A-DR/DQ基因分型。用甲基化特异性聚合酶链式反应检测CITA甲基化。结果：UC-CRC患者携带DR17或DR13等位基因的可能性明显高于UC对照组(P
Objectives: Patients with ulcerative colitis are at risk for colorectal cancer (CRC). Although prior studies have shown a link between HLA genotypes and ulcerative colitis (UC) susceptibility, none have investigated HLA genotypes and UC-CRC. We therefore investigated HLA-DR/DQ alleles in UC-CRC cases and UC-controls. Furthermore, since methylation of the Class II transactivator (CIITA) gene may silence HLA expression in tumours, we correlated HLA allele frequencies with CIITA gene methylation and HLA-DR expression.Methods: Cases and controls were matched for duration/extent of ulcerative colitis, age, ethnicity and gender, but not for primary sclerosing cholangitis (PSC). DNA was extracted from archived tissue blocks from 114 UC-CRC cases and 114 UC-controls. HLA-DR/DQ genotyping was performed using sequence-specific-oligonucleotide polymerase chain reaction (SSO-PCR). CIITA methylation was determined using methylation-specific PCR. HLA-DR immunohistochemistry was done following standard protocols.Results: UC-CRC cases were more likely than UC-controls to carry the DR17 or DR13 alleles (p