与乳腺癌特异性生存相关的常见种系多态性。
Common germline polymorphisms associated with breast cancer-specific survival.
作者信息
Pirie Ailith, Guo Qi, Kraft Peter, Canisius Sander, Eccles Diana M, Rahman Nazneen, Nevanlinna Heli, Chen Constance, Khan Sofia, Tyrer Jonathan, Bolla Manjeet K, Wang Qin, Dennis Joe, Michailidou Kyriaki, Lush Michael, Dunning Alison M, Shah Mitul, Czene Kamila, Darabi Hatef, Eriksson Mikael, Lambrechts Dieter, Weltens Caroline, Leunen Karin, van Ongeval Chantal, Nordestgaard Børge G, Nielsen Sune F, Flyger Henrik, Rudolph Anja, Seibold Petra, Flesch-Janys Dieter, Blomqvist Carl, Aittomäki Kristiina, Fagerholm Rainer, Muranen Taru A, Olsen Janet E, Hallberg Emily, Vachon Celine, Knight Julia A, Glendon Gord, Mulligan Anna Marie, Broeks Annegien, Cornelissen Sten, Haiman Christopher A, Henderson Brian E, Schumacher Frederick, Le Marchand Loic, Hopper John L, Tsimiklis Helen, Apicella Carmel, Southey Melissa C, Cross Simon S, Reed Malcolm Wr, Giles Graham G, Milne Roger L, McLean Catriona, Winqvist Robert, Pylkäs Katri, Jukkola-Vuorinen Arja, Grip Mervi, Hooning Maartje J, Hollestelle Antoinette, Martens John Wm, van den Ouweland Ans Mw, Marme Federick, Schneeweiss Andreas, Yang Rongxi, Burwinkel Barbara, Figueroa Jonine, Chanock Stephen J, Lissowska Jolanta, Sawyer Elinor J, Tomlinson Ian, Kerin Michael J, Miller Nicola, Brenner Hermann, Butterbach Katja, Holleczek Bernd, Kataja Vesa, Kosma Veli-Matti, Hartikainen Jaana M, Li Jingmei, Brand Judith S, Humphreys Keith, Devilee Peter, Tollenaar Robert Aem, Seynaeve Caroline, Radice Paolo, Peterlongo Paolo, Manoukian Siranoush, Ficarazzi Filomena, Beckmann Matthias W, Hein Alexander, Ekici Arif B, Balleine Rosemary, Phillips Kelly-Anne, Benitez Javier, Zamora M Pilar, Perez Jose Ignacio Arias, Menéndez Primitiva, Jakubowska Anna, Lubinski Jan, Gronwald Jacek, Durda Katarzyna, Hamann Ute, Kabisch Maria, Ulmer Hans Ulrich, Rüdiger Thomas, Margolin Sara, Kristensen Vessela, Nord Siljie, Evans D Gareth, Abraham Jean, Earl Helena, Poole Christopher J, Hiller Louise, Dunn Janet A, Bowden Sarah, Yang Rose, Campa Daniele, Diver W Ryan, Gapstur Susan M, Gaudet Mia M, Hankinson Susan, Hoover Robert N, Hüsing Anika, Kaaks Rudolf, Machiela Mitchell J, Willett Walter, Barrdahl Myrto, Canzian Federico, Chin Suet-Feung, Caldas Carlos, Hunter David J, Lindstrom Sara, Garcia-Closas Montserrat, Couch Fergus J, Chenevix-Trench Georgia, Mannermaa Arto, Andrulis Irene L, Hall Per, Chang-Claude Jenny, Easton Douglas F, Bojesen Stig E, Cox Angela, Fasching Peter A, Pharoah Paul Dp, Schmidt Marjanka K
机构信息
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK.
出版信息
Breast Cancer Res. 2015 Apr 22;17(1):58. doi: 10.1186/s13058-015-0570-7.
INTRODUCTION
Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.
METHODS
A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.
RESULTS
Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.
CONCLUSIONS
Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.
引言
先前的研究已经确定了与乳腺癌生存名义上相关的常见种系变异。这些关联在进一步的研究中尚未得到广泛重复验证。本研究的目的是利用来自乳腺癌协会联盟八项乳腺癌生存全基因组关联研究（GWAS）汇总分析的数据，评估先前报道的单核苷酸多态性（SNP）与乳腺癌特异性生存的关联。
方法
对先前发表的所有关于常见种系变异与三种生存结局（乳腺癌特异性生存、总生存和无病生存）之间的关联进行了文献综述。纳入所有达到名义显著性水平P值<0.05的关联。在对超过37000例乳腺癌病例的汇总分析中，评估先前报道的与至少一种生存结局名义上相关的单核苷酸多态性与乳腺癌特异性生存的关联。根据报道的效应方向，使用单侧检验评估先前的关联。
结果
在荟萃分析中评估了来自先前发表的45篇文献中的56个变异。其中54个在37954例乳腺癌病例的完整数据集中进行评估，有2900例事件发生，另外两个变异在30000例样本的缩减样本量中进行评估，以确保与先前发表的研究独立。与零假设下预期的2.8个相比，在汇总的GWAS数据中有5个变异达到名义显著性（P<0.05）。另外7个变异与雌激素受体（ER）阳性疾病相关（P<0.05）。
结论
尽管没有变异达到全基因组显著性（P<5×10⁻⁸），但这些结果表明有一些证据支持候选常见种系变异与乳腺癌预后之间存在关联。有必要开展来自跨国合作的更大规模研究，以提高在更严格显著性水平下检测常见变异与预后之间关联的能力。
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