Analysis of HLA class I-II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer.

Z Gamzatova, L Villabona, H van der Zanden, G W Haasnoot, E Andersson, R Kiessling, B Seliger, L Kanter, T Dalianis, K Bergfeldt, G V Masucci
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引用次数: 19

Abstract

In solid tumors, human leucocyte antigen (HLA)-A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA-A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA-A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III-IV was found. Thirty-two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 loci by the polymerase chain reaction/sequence-specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA-A1 and HLA-A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA-A3 was decreased. HLA-A2 homozygotes were twofold higher in patients. The A2-B8 haplotype was significantly increased (corrected P value). A2-B5, A2-B15, A2-DRB1*03, A2-DRB1*04, A2-B15-Cw3, and A2-B8-DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non-corrected analysis. HLA-B15 and HLA-Cw3 were only present in HLA-A2-positive patients showing that the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations.

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1例晚期卵巢癌患者HLA I-II类单倍型频率及分离分析。
在实体瘤中,人白细胞抗原(HLA)-A2被认为是一个危险因素和一个负面预后因素。HLA-A2等位基因在斯堪的纳维亚半岛有很高的患病率;在欧洲,它随着纬度和卵巢癌死亡率的变化而降低。此外,发现HLA-A2等位基因与III-IV期卵巢浆液性腺癌的严重预后相关。采用聚合酶链反应/序列特异性引物法对32例瑞典无亲缘关系的复发或进展性卵巢癌女性进行HLA-A、HLA-B、HLA-Cw和HLA-DRB1位点的基因型分析。由荷兰莱顿骨髓捐献者全球登记协调中心提供的瑞典健康骨髓捐献者HLA等位基因频率作为对照。当这组上皮性卵巢癌患者与健康的瑞典供者进行比较时,HLA-A1和HLA-A2基因/表型的频率在卵巢癌患者中出现增加,而HLA-A3减少,尽管没有统计学意义。HLA-A2纯合子在患者中高出两倍。A2-B8单倍型显著增加(校正P值)。A2-B5、A2-B15、A2-DRB1*03、A2-DRB1*04、A2-B15- cw3、A2-B8-DRB1*03仅作为单一、非校正分析时才存在优势比、下置信区间大于1的水平和显著P值。HLA-B15和HLA-Cw3仅在hla - a2阳性患者中存在,表明HLA-A2-HLA-Cw3和HLA-B15单倍型存在分离。在这个选择的晚期疾病队列中,有迹象表明HLA I类和II类基因/单倍型的异常过度代表以及HLA- a2 -HLA- cw3和HLA- b15单倍型的分离。这些发现是描述性分析,需要对更大范围的卵巢癌患者进行进一步调查,以建立预后关联。
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Tissue antigens
Tissue antigens 医学-病理学
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