IL-6 variant is associated with metastasis in breast cancer patients.
IL-6 variant is associated with metastasis in breast cancer patients.
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DOI：
10.1371/journal.pone.0181725
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Xia F
中科院分区：
文献类型：
--
作者：
Abana CO;Bingham BS;Cho JH;Graves AJ;Koyama T;Pilarski RT;Chakravarthy AB;Xia F
虽然肿瘤转移仍然是死亡率的重要驱动因素，但增加转移风险的遗传因素尚未完全确定。白细胞介素6（IL-6）已成为乳腺癌进展中的一个重要因素，IL-6单核苷酸多态性（SNP）变体显示影响生存。我们假设乳腺癌患者IL-6启动子rs 1800795位点的SNPs与远处转移相关。我们使用范德比尔特大学医学中心的BioVU（一个与合成衍生物数据库中的去识别电子医疗记录相关联的基因组生物库）进行了一项初步病例对照研究，以确定可以预测任何实体瘤（包括乳腺癌）向任何部位转移疾病的发生的种系SNP。我们确定了IL-6：rs 1800795中的SNP具有显著性，并使用来自俄亥俄州州立大学Wexner医学中心的乳腺癌伴和不伴转移的单独配对队列评估了这一发现。最初的研究表明，GG相对于CG在rs 1800795（OR 1.52; 95% CI 1.14-2.02; p = 0.004）与转移的发展显著相关。在俄亥俄州州立大学队列中也观察到了这种关联（OR 2.23; 95% CI 1.06-4.71; p = 0.001）。rs 1800795状态与任何患者或肿瘤特征（包括雌激素受体状态）之间没有显着关系。这些发现表明IL-6：rs 1800795的GG SNP可能指示原发性乳腺癌转移的风险增加。在更大的人群中进行进一步的研究是必要的，因为在GG携带者中可能会采用先进的筛查和预防性干预。
Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases. We performed an initial case-control study using Vanderbilt University Medical Center’s BioVU, a genomic biobank linked to de-identified electronic medical records in the Synthetic Derivative database, to identify germline SNPs that may predict the development of metastatic disease to any site from any solid tumor including breast cancer. We identified a SNP in IL-6: rs1800795 to be of significance and evaluated this finding using a separate, matched-pair cohort of breast cancer patients with and without metastases from The Ohio State University Wexner Medical Center. The initial study suggested that GG relative to CG at rs1800795 (OR 1.52; 95% CI 1.14–2.02; p = 0.004) was significantly associated with the development of metastases. This association was also observed in the Ohio State University cohort (OR 2.23; 95% CI 1.06–4.71; p = 0.001). There were no significant relationships between rs1800795 status and any patient or tumor characteristics, including estrogen receptor status. These findings suggest that GG SNP at IL-6: rs1800795 may indicate an increased risk of metastasis of primary breast cancer. Further studies in larger population sets are warranted as advanced screening and prophylactic intervention might be employed in GG carriers.