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Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker

机译：整合素基因和乳腺癌中预测的microRNA结合位点的多态性：ITGB4作为预后标志物

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Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3′ untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19–3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21–3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
机译：整联蛋白控制细胞对细胞外基质的附着，并在介导细胞增殖，迁移和存活中起重要作用。许多重要的与癌症相关的整联蛋白基因可以通过与3'非翻译区域中靶位点结合的microRNA（miRNA）进行调控。我们检查了六个整合素基因（ITGA3，ITGA6，ITGAv，ITGB3，ITGB4和ITGB5）的预测miRNA靶位点中单核苷酸多态性（SNP）对乳腺癌（BC）风险和临床结局的影响。在749例瑞典BC病例中对6个SNP进行了基因分型，这些病例具有详细的临床数据和长达15年的随访以及1493个匹配的对照。我们评估了基因型与BC风险和临床肿瘤特征之间的关联。比较不同亚组之间的生存概率。作为一个新颖的发现，一些SNP似乎与激素受体状态有关。观察到ITGB4基因中SNP rs743554的A等位基因与雌激素受体阴性肿瘤之间的关联最强[比值2.09，95％置信区间（CI）1.19-3.67]。相同的SNP与生存率相关。与野生型基因型携带者相比，A等位基因携带者的生存期较差（危险比2.11，95％CI 1.21–3.68）。不良的存活率与侵袭性肿瘤特征显着相关：高级别，淋巴结转移和晚期。没有一个SNP与BC风险显着相关。由于ITGB4 SNP似乎会影响肿瘤的侵袭性和生存率，因此在临床上可能具有预后价值。

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  • 来源
    《Carcinogenesis》 |2008年第7期|p.1394-1399|共6页
  • 作者

    Annika Brendle1 Haixin Lei15 Andreas Brandt1 Robert Johansson2 Kerstin Enquist3 Roger Henriksson2 Kari Hemminki14 Per Lenner2 and Asta Försti14*;

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    1Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany 2Department of Oncology, Norrlands University Hospital, 90187 Umeå, Sweden 3Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, 90185 Umeå, Sweden 4Center for Family and Community Medicine, Karolinska Institute, 14183 Huddinge, Sweden 5Present address: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB R505, Boston, MA 02115, USA;

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