Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.
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DOI：
10.1093/jnci/djv219
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Ben Zhang;X. Shu;Ryan J. Delahanty;Chenjie Zeng;K. Michailidou;M. Bolla;Qin Wang;J. Dennis;W. Wen;J. Long;Chun Li;A. Dunning;J. Chang-Claude;M. Shah;B. Perkins;K. Czene;Hatef Darabi;M. Eriksson;S. Bojesen;B. Nordestgaard;S. F. Nielsen;H. Flyger;D. Lambrechts;P. Neven;H. Wildiers;G. Floris;M. Schmidt;M. Rookus;Katja van den Hurk;Wim L. A. M. de Kort;F. Couch;J. Olson;Emily J. Hallberg;C. Vachon;A. Rudolph;P. Seibold;D. Flesch-Janys;J. Peto;I. dos-Santos-Silva;O. Fletcher;N. Johnson;H. Nevanlinna;T. Muranen;K. Aittomäki;C. Blomqvist;Jingmei Li;K. Humphreys;Judith S. Brand;P. Guénel;Thérèse Truong;E. Cordina-Duverger;F. Menegaux;B. Burwinkel;F. Marmé;Rongxi Yang;H. Surowy;J. Benítez;M. P. Zamora;J. I. Perez;A. Cox;S. Cross;M. Reed;I. Andrulis;J. Knight;G. Glendon;S. Tchatchou;E. Sawyer;I. Tomlinson;M. Kerin;N. Miller;G. Chenevix-Trench;C. Haiman;B. E. Henderson;F. Schumacher;L. Marchand;A. Lindblom;S. Margolin;M. Hooning;John W. M. Martens;M. Tilanus-Linthorst;J. Collée;J. Hopper;M. Southey;H. Tsimiklis;C. Apicella;S. Slager;A. Toland;C. Ambrosone;D. Yannoukakos;Graham G. Giles;R. Milne;C. Mclean;P. Fasching;L. Haeberle;A. Ekici;M. W. Beckmann;H. Brenner;A. K. Dieffenbach;V. Arndt;C. Stegmaier;Anthony J. Swerdlow;A. Ashworth;N. Orr;Michael P. Jones;J. Figueroa;M. García-Closas;L. Brinton;J. Lissowska;M. Dumont;R. Winqvist;K. Pylkäs;A. Jukkola-Vuorinen;Mervi Grip;H. Brauch;T. Brüning;Y. Ko;P. Peterlongo;S. Manoukian;B. Bonanni;P. Radice;N. Bogdanova;N. Antonenkova;T. Dörk;A. Mannermaa;V. Kataja;V. Kosma;Jaana M. Hartikainen;P. Devilee;C. Seynaeve;C. V. van Asperen;A. Jakubowska;J. Lubiński;Katarzyna Jaworska–Bieniek;K. Durda;U. Hamann;Diana Torres;R. Schmutzler;S. Neuhausen;H. Anton-Culver;V. Kristensen;Grethe I. Grenaker Alnæs;B. Pierce;P. Kraft;U. Peters;S. Lindstrom;D. Seminara;S. Burgess;Habibul Ahsan;A. Whittemore;Esther M. John;M. Gammon;K. Malone;D. Tessier;Daniel Vincent;F. Bacot;C. Luccarini;C. Baynes;Shahana Ahmed;M. Maranian;C. Healey;A. González-Neira;G. Pita;M. R. Alonso;N. Álvarez;D. Herrero;Paul D. P. Pharoah;J. Simard;P. Hall;D. J. Hunter;D. Easton;W. Zheng
中科院分区：
文献类型：
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作者：
Ben Zhang;X. Shu;Ryan J. Delahanty;Chenjie Zeng;K. Michailidou;M. Bolla;Qin Wang;J. Dennis;W. Wen;J. Long;Chun Li;A. Dunning;J. Chang-Claude;M. Shah;B. Perkins;K. Czene;Hatef Darabi;M. Eriksson;S. Bojesen;B. Nordestgaard;S. F. Nielsen;H. Flyger;D. Lambrechts;P. Neven;H. Wildiers;G. Floris;M. Schmidt;M. Rookus;Katja van den Hurk;Wim L. A. M. de Kort;F. Couch;J. Olson;Emily J. Hallberg;C. Vachon;A. Rudolph;P. Seibold;D. Flesch-Janys;J. Peto;I. dos-Santos-Silva;O. Fletcher;N. Johnson;H. Nevanlinna;T. Muranen;K. Aittomäki;C. Blomqvist;Jingmei Li;K. Humphreys;Judith S. Brand;P. Guénel;Thérèse Truong;E. Cordina-Duverger;F. Menegaux;B. Burwinkel;F. Marmé;Rongxi Yang;H. Surowy;J. Benítez;M. P. Zamora;J. I. Perez;A. Cox;S. Cross;M. Reed;I. Andrulis;J. Knight;G. Glendon;S. Tchatchou;E. Sawyer;I. Tomlinson;M. Kerin;N. Miller;G. Chenevix-Trench;C. Haiman;B. E. Henderson;F. Schumacher;L. Marchand;A. Lindblom;S. Margolin;M. Hooning;John W. M. Martens;M. Tilanus-Linthorst;J. Collée;J. Hopper;M. Southey;H. Tsimiklis;C. Apicella;S. Slager;A. Toland;C. Ambrosone;D. Yannoukakos;Graham G. Giles;R. Milne;C. Mclean;P. Fasching;L. Haeberle;A. Ekici;M. W. Beckmann;H. Brenner;A. K. Dieffenbach;V. Arndt;C. Stegmaier;Anthony J. Swerdlow;A. Ashworth;N. Orr;Michael P. Jones;J. Figueroa;M. García-Closas;L. Brinton;J. Lissowska;M. Dumont;R. Winqvist;K. Pylkäs;A. Jukkola-Vuorinen;Mervi Grip;H. Brauch;T. Brüning;Y. Ko;P. Peterlongo;S. Manoukian;B. Bonanni;P. Radice;N. Bogdanova;N. Antonenkova;T. Dörk;A. Mannermaa;V. Kataja;V. Kosma;Jaana M. Hartikainen;P. Devilee;C. Seynaeve;C. V. van Asperen;A. Jakubowska;J. Lubiński;Katarzyna Jaworska–Bieniek;K. Durda;U. Hamann;Diana Torres;R. Schmutzler;S. Neuhausen;H. Anton-Culver;V. Kristensen;Grethe I. Grenaker Alnæs;B. Pierce;P. Kraft;U. Peters;S. Lindstrom;D. Seminara;S. Burgess;Habibul Ahsan;A. Whittemore;Esther M. John;M. Gammon;K. Malone;D. Tessier;Daniel Vincent;F. Bacot;C. Luccarini;C. Baynes;Shahana Ahmed;M. Maranian;C. Healey;A. González-Neira;G. Pita;M. R. Alonso;N. Álvarez;D. Herrero;Paul D. P. Pharoah;J. Simard;P. Hall;D. J. Hunter;D. Easton;W. Zheng
流行病学研究已经将成年身高与女性患乳腺癌的风险联系起来。然而，这种关联的程度，特别是乳腺癌的亚型，尚未确定。此外，该协会的机制仍不清楚。我们进行了一项荟萃分析，调查身高和乳腺癌风险之间的关系，使用的数据来自159个前瞻性队列，共计5216302名妇女，包括113178起事件。在46325例病例患者和42482例对照患者的个体水平数据的联盟中，我们使用包括168个身高相关变异的遗传评分作为工具进行了孟德尔随机化分析。在第二个联盟中，使用来自16003例病例患者和41335例对照患者的汇总统计数据进一步评估了这种关联。结果：在前瞻性研究的荟萃分析中，身高每增加10 cm，乳腺癌的合并相对危险度为1.17（95%置信区间[CI] = 1.15 - 1.19）。在孟德尔随机化分析中，遗传预测身高每增加10 cm，乳腺癌的比值比在第一联盟中为1.22（95%CI = 1.13至1.32），在第二联盟中为1.21（95%CI = 1.05至1.39）。这种关联在绝经前和绝经后妇女中均被发现，但仅限于激素受体阳性乳腺癌。对身高相关变异的分析在调整多重比较后确定了8个与乳腺癌风险相关的新位点，包括1q21.2、DNAJC 27和CCDC 91的3个位点，全基因组显著性水平P < 5×10（-8）。结论：我们的研究提供了强有力的证据，成年身高是女性乳腺癌的危险因素，某些影响成年身高的遗传因素和生物学途径在乳腺癌的病因学中具有重要作用。
BACKGROUND Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. RESULTS The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8). CONCLUSIONS Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.