Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival
Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival
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DOI：
10.1007/s10549-011-1765-y
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发表时间：
2011
影响因子：
3.8
通讯作者：
Verena Varadi;Melanie Bevier;E. Grzybowska;R. Johansson;Kerstin Enquist-Olsson;R. Henriksson;D. Butkiewicz;J. Pamuła-Piłat;K. Tęcza;K. Hemminki;P. Lenner;A. Försti
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文献类型：
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作者：
Verena Varadi;Melanie Bevier;E. Grzybowska;R. Johansson;Kerstin Enquist-Olsson;R. Henriksson;D. Butkiewicz;J. Pamuła-Piłat;K. Tęcza;K. Hemminki;P. Lenner;A. Försti
染色体不稳定性是许多癌症的标志，并且其具有预测癌症患者的临床结果的潜力。我们假设，在染色体稳定和不稳定乳腺肿瘤之间表达状态不同的基因代表了用于鉴定预测乳腺癌（BC）风险、疾病进展和生存的遗传变异的靶基因。我们使用了一个已发表的38个与染色体不稳定性相关的基因列表，作为搜索潜在功能和信息标记单核苷酸多态性（SNP）的基础。结果，在783例瑞典BC病例的人群系列中，对16个基因中的33个SNP进行了基因分型。ALCAM基因中的两个SNP与BC特异性生存相关。对于次要等位基因的纯合携带者，rs 1044243的HR为4.35（95% CI 1.34-14.18），rs 1157的HR为3.42（95% CI 1.32-8.83）。对于CCL 18 SNP rs 14304的次要等位基因携带者，我们观察到与侵袭性肿瘤特征显著相关：大肿瘤大小（OR 1.53，95%CI 1.10-2.14），阳性淋巴结转移（OR 1.75，95%CI 1.02-3.00）和高分期（OR 1.37，95%CI 1.02-1.85）。在一个由506例家族性/早发性BC病例组成的波兰人群中，没有观察到ALCAM SNP与无事件生存率的相关性，也没有观察到CCL 18 SNP与肿瘤特征的相关性，这表明在瑞典人群中的偶然发现或散发性和家族性/早发性BC之间基于人群或病因学的差异。
Chromosomal instability is a hallmark of many cancers and it has a potential to predict clinical outcome of a cancer patient. We hypothesized that genes whose expression status differs between chromosomal stable and unstable breast tumors represent target genes for the identification of genetic variants predicting breast cancer (BC) risk, disease progression, and survival. We used a published list of 38 genes associated with chromosomal instability as a basis for searching potentially functional and informative tagging single nucleotide polymorphisms (SNPs). As a result, 33 SNPs in 16 genes were genotyped in a population-based series of 783 Swedish BC cases. Two SNPs in theALCAMgene associated with BC-specific survival. For rs1044243, the HR was 4.35 (95% CI 1.34–14.18), and for rs1157, the HR was 3.42 (95% CI 1.32–8.83) for the homozygous carriers of the minor alleles. For the minor allele carriers ofCCL18SNP rs14304, we observed a significant association with aggressive tumor characteristics: large tumor size (OR 1.53, 95% CI 1.10–2.14), positive lymph node metastasis (OR 1.75, 95% CI 1.02–3.00), and high stage (OR 1.37, 95% CI 1.02–1.85). In a Polish population consisting of 506 familial/early onset BC cases, no association with event-free survival for theALCAMSNPs nor any association with tumor characteristics for theCCL18SNP were observed, suggesting either a chance finding in the Swedish population or population-based or etiological differences between sporadic and familial/early onset BC.