Common variants in breast cancer risk loci predispose to distinct tumor subtypes.
Common variants in breast cancer risk loci predispose to distinct tumor subtypes.
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DOI：
10.1186/s13058-021-01484-x
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发表时间：
2022-01-04
期刊：
影响因子：
--
通讯作者：
Chatterjee N
中科院分区：
文献类型：
--
作者：
Ahearn TU;Zhang H;Michailidou K;Milne RL;Bolla MK;Dennis J;Dunning AM;Lush M;Wang Q;Andrulis IL;Anton-Culver H;Arndt V;Aronson KJ;Auer PL;Augustinsson A;Baten A;Becher H;Behrens S;Benitez J;Bermisheva M;Blomqvist C;Bojesen SE;Bonanni B;Børresen-Dale AL;Brauch H;Brenner H;Brooks-Wilson A;Brüning T;Burwinkel B;Buys SS;Canzian F;Castelao JE;Chang-Claude J;Chanock SJ;Chenevix-Trench G;Clarke CL;NBCS Collaborators;Collée JM;Cox A;Cross SS;Czene K;Daly MB;Devilee P;Dörk T;Dwek M;Eccles DM;Evans DG;Fasching PA;Figueroa J;Floris G;Gago-Dominguez M;Gapstur SM;García-Sáenz JA;Gaudet MM;Giles GG;Goldberg MS;González-Neira A;Alnæs GIG;Grip M;Guénel P;Haiman CA;Hall P;Hamann U;Harkness EF;Heemskerk-Gerritsen BAM;Holleczek B;Hollestelle A;Hooning MJ;Hoover RN;Hopper JL;Howell A;ABCTB Investigators;kConFab/AOCS Investigators;Jakimovska M;Jakubowska A;John EM;Jones ME;Jung A;Kaaks R;Kauppila S;Keeman R;Khusnutdinova E;Kitahara CM;Ko YD;Koutros S;Kristensen VN;Krüger U;Kubelka-Sabit K;Kurian AW;Kyriacou K;Lambrechts D;Lee DG;Lindblom A;Linet M;Lissowska J;Llaneza A;Lo WY;MacInnis RJ;Mannermaa A;Manoochehri M;Margolin S;Martinez ME;McLean C;Meindl A;Menon U;Nevanlinna H;Newman WG;Nodora J;Offit K;Olsson H;Orr N;Park-Simon TW;Patel AV;Peto J;Pita G;Plaseska-Karanfilska D;Prentice R;Punie K;Pylkäs K;Radice P;Rennert G;Romero A;Rüdiger T;Saloustros E;Sampson S;Sandler DP;Sawyer EJ;Schmutzler RK;Schoemaker MJ;Schöttker B;Sherman ME;Shu XO;Smichkoska S;Southey MC;Spinelli JJ;Swerdlow AJ;Tamimi RM;Tapper WJ;Taylor JA;Teras LR;Terry MB;Torres D;Troester MA;Vachon CM;van Deurzen CHM;van Veen EM;Wagner P;Weinberg CR;Wendt C;Wesseling J;Winqvist R;Wolk A;Yang XR;Zheng W;Couch FJ;Simard J;Kraft P;Easton DF;Pharoah PDP;Schmidt MK;García-Closas M;Chatterjee N
全基因组关联研究 (GWAS) 已经确定了多种常见的乳腺癌易感性变异。其中许多变异与雌激素受体 (ER) 状态存在差异关联，但这些变异与其他肿瘤特征和内在分子亚型的关系尚不清楚。在 106,571 例浸润性乳腺癌病例和 95,762 名欧洲血统对照患者中，以及之前 GWAS 中发现的 173 种乳腺癌变异数据，我们使用新型两阶段多级 Logistic 回归模型来评估与多个肿瘤特征（ER、孕激素受体 (PR)、人表皮生长因子受体 2 (HER2) 和级别）相关的变异，这些变异相互调整，并与内在样亚型相关。 173 个变异中的 85 个与至少一种肿瘤特征相关（错误发现率 < 5%），最常见的是 ER 和分级，其次是 PR 和 HER2。内在样亚型模型发现，几乎所有这些变异（85 种中的 83 种）在 p<0.05 时与至少一种管腔样亚型的风险相关，大约一半的变异（85 种中的 41 种）与至少一种非管腔亚型的风险相关，其中包括 32 种与三阴性 (TN) 疾病相关的变异。十种变异与不同程度的所有亚型风险相关。五种变异与管腔 A 样和 TN 亚型相反方向的风险相关。该报告证明了乳腺癌易感性变异的病因异质性高度复杂，可以为亚型特异性风险预测的研究提供信息。在线版本包含可在 10.1186/s13058-021-01484-x 获取的补充材料。
Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction. The online version contains supplementary material available at 10.1186/s13058-021-01484-x.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
30.8
作者：
Dunning AM;Michailidou K;Kuchenbaecker KB;Thompson D;French JD;Beesley J;Healey CS;Kar S;Pooley KA;Lopez-Knowles E;Dicks E;Barrowdale D;Sinnott-Armstrong NA;Sallari RC;Hillman KM;Kaufmann S;Sivakumaran H;Moradi Marjaneh M;Lee JS;Hills M;Jarosz M;Drury S;Canisius S;Bolla MK;Dennis J;Wang Q;Hopper JL;Southey MC;Broeks A;Schmidt MK;Lophatananon A;Muir K;Beckmann MW;Fasching PA;Dos-Santos-Silva I;Peto J;Sawyer EJ;Tomlinson I;Burwinkel B;Marme F;Guénel P;Truong T;Bojesen SE;Flyger H;González-Neira A;Perez JI;Anton-Culver H;Eunjung L;Arndt V;Brenner H;Meindl A;Schmutzler RK;Brauch H;Hamann U;Aittomäki K;Blomqvist C;Ito H;Matsuo K;Bogdanova N;Dörk T;Lindblom A;Margolin S;Kosma VM;Mannermaa A;Tseng CC;Wu AH;Lambrechts D;Wildiers H;Chang-Claude J;Rudolph A;Peterlongo P;Radice P;Olson JE;Giles GG;Milne RL;Haiman CA;Henderson BE;Goldberg MS;Teo SH;Yip CH;Nord S;Borresen-Dale AL;Kristensen V;Long J;Zheng W;Pylkäs K;Winqvist R;Andrulis IL;Knight JA;Devilee P;Seynaeve C;Figueroa J;Sherman ME;Czene K;Darabi H;Hollestelle A;van den Ouweland AM;Humphreys K;Gao YT;Shu XO;Cox A;Cross SS;Blot W;Cai Q;Ghoussaini M;Perkins BJ;Shah M;Choi JY;Kang D;Lee SC;Hartman M;Kabisch M;Torres D;Jakubowska A;Lubinski J;Brennan P;Sangrajrang S;Ambrosone CB;Toland AE;Shen CY;Wu PE;Orr N;Swerdlow A;McGuffog L;Healey S;Lee A;Kapuscinski M;John EM;Terry MB;Daly MB;Goldgar DE;Buys SS;Janavicius R;Tihomirova L;Tung N;Dorfling CM;van Rensburg EJ;Neuhausen SL;Ejlertsen B;Hansen TV;Osorio A;Benitez J;Rando R;Weitzel JN;Bonanni B;Peissel B;Manoukian S;Papi L;Ottini L;Konstantopoulou I;Apostolou P;Garber J;Rashid MU;Frost D;EMBRACE;Izatt L;Ellis S;Godwin AK;Arnold N;Niederacher D;Rhiem K;Bogdanova-Markov N;Sagne C;Stoppa-Lyonnet D;Damiola F;GEMO Study Collaborators;Sinilnikova OM;Mazoyer S;Isaacs C;Claes KB;De Leeneer K;de la Hoya M;Caldes T;Nevanlinna H;Khan S;Mensenkamp AR;HEBON;Hooning MJ;Rookus MA;Kwong A;Olah E;Diez O;Brunet J;Pujana MA;Gronwald J;Huzarski T;Barkardottir RB;Laframboise R;Soucy P;Montagna M;Agata S;Teixeira MR;kConFab Investigators;Park SK;Lindor N;Couch FJ;Tischkowitz M;Foretova L;Vijai J;Offit K;Singer CF;Rappaport C;Phelan CM;Greene MH;Mai PL;Rennert G;Imyanitov EN;Hulick PJ;Phillips KA;Piedmonte M;Mulligan AM;Glendon G;Bojesen A;Thomassen M;Caligo MA;Yoon SY;Friedman E;Laitman Y;Borg A;von Wachenfeldt A;Ehrencrona H;Rantala J;Olopade OI;Ganz PA;Nussbaum RL;Gayther SA;Nathanson KL;Domchek SM;Arun BK;Mitchell G;Karlan BY;Lester J;Maskarinec G;Woolcott C;Scott C;Stone J;Apicella C;Tamimi R;Luben R;Khaw KT;Helland Å;Haakensen V;Dowsett M;Pharoah PD;Simard J;Hall P;García-Closas M;Vachon C;Chenevix-Trench G;Antoniou AC;Easton DF;Edwards SL
通讯作者：
Edwards SL
影响因子：
7.3
作者：
Bombonati, Alessandro;Sgroi, Dennis C.
通讯作者：
Sgroi, Dennis C.
影响因子：
8.8
作者：
Rajakariar, R.;Walker, R. A.
通讯作者：
Walker, R. A.
影响因子：
10.3
作者：
Meeks, Huong D.;Song, Honglin;Goldgar, David E.
通讯作者：
Goldgar, David E.