评估 94 个单核苷酸多态性风险评分在 SIGNAL/PHARE 前瞻性队列中早期乳腺癌的预后作用：与临床病理特征和结局无关。
Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.
机构信息
Hôpital Jean-Minjoz, Centre Hospitalier Universitaire, UMR 1098 INSERM-EFS-Université de Bourgogne Franche-Comté, Boulevard Fleming, 25000, Besançon, France.
Department of Medical Oncology, University Hospital Jean Minjoz, 3, boulevard Alexandre Fleming, 25030, Besancon Cedex, France.
出版信息
Breast Cancer Res. 2017 Aug 22;19(1):98. doi: 10.1186/s13058-017-0888-4.
BACKGROUND
Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer.
METHODS
A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS.
RESULTS
The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival.
CONCLUSIONS
In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis.
TRIAL REGISTRATION
PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.
背景
全基因组关联研究（GWAS）迄今为止已确定了 94 个与乳腺癌发病风险相关的遗传变异（单核苷酸多态性（SNP））。可以计算基于 94 个风险等位基因的综合效应的评分，以衡量乳腺癌的总体风险。我们旨在检验以下假设：基于 94 个 SNP 的风险评分与早期乳腺癌的临床病理特征、乳腺癌亚型和结局相关。
方法
在 PHARE 和 SIGNAL 前瞻性病例队列的 8703 名患者中计算了 94-SNP 风险评分。该评分是基于 94 个选定 SNP 的遗传风险等位基因总数。临床数据和结局均前瞻性登记。基因分型来自 GWAS。
结果
8703 例早期乳腺癌患者的中位数 94-SNP 风险评分为 77.5（范围：58.1-97.6）。风险评分与常见的预后和预测因素（年龄；肿瘤、淋巴结、转移（TNM）状态；Scarff-Bloom-Richardson 分级；炎症特征；雌激素受体状态；孕激素受体状态；人表皮生长因子受体 2（HER2）状态）无关，也与乳腺癌亚型无关。94-SNP 风险评分与总生存或无病生存等结局无关。
结论
在 8703 例前瞻性病例队列中，基于 94 个 SNP 的风险评分与乳腺癌特征、癌症亚型或患者结局无关。如果我们假设乳腺癌的预后和亚型由体质遗传因素决定，那么我们的结果表明，基于乳腺癌风险相关 SNP 的评分与预后无关。
试验注册
PHARE 队列：NCT00381901，2006 年 9 月 26 日-SIGNAL 队列：INCa RECF1098，2009 年 1 月 28 日。
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