Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.
Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.
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DOI：
10.1038/s41467-021-21288-z
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发表时间：
2021-02-12
影响因子：
16.6
通讯作者：
Sakoda LC
中科院分区：
文献类型：
--
作者：
Graff RE;Cavazos TB;Thai KK;Kachuri L;Rashkin SR;Hoffman JD;Alexeeff SE;Blatchins M;Meyers TJ;Leong L;Tai CG;Emami NC;Corley DA;Kushi LH;Ziv E;Van Den Eeden SK;Jorgenson E;Hoffmann TJ;Habel LA;Witte JS;Sakoda LC
即使是不同的癌症类型也有共同的生物学特征。在这里，我们调查了来自成人健康和衰老遗传流行病学研究队列（16,012 例，50,552 例对照）和英国生物库（48,969 例，359,802 例对照）的欧洲血统个体的 16 种癌症的多基因风险评分 (PRS) 特异性多效性。在队列中，每个 PRS 都在多变量逻辑回归模型中针对所有其他癌症类型进行评估。然后对不同队列的结果进行荟萃分析。经过多次测试校正后发现 10 个正向跨癌关联和 1 个反向跨癌关联。两对显示双向关联；黑色素瘤PRS与口腔/咽癌呈正相关，反之亦然；而肺癌PRS与口腔/咽癌呈正相关，口腔/咽癌PRS与肺癌呈负相关。总体而言，我们验证了已知的并发现了以前未报告的多效性模式，这些模式有可能为风险预测、共同病因学和精准癌症预防策略的研究提供信息。虽然已经确定了癌症类型之间共享的遗传位点，但多基因风险评分的跨癌症关系尚未得到充分研究。在这里，作者开发了两个大型队列中 16 种癌症的多基因风险评分，并确定了正向和反向跨癌症关联。
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies. While genetic loci shared between cancer types have been identified, cross-cancer relationships for polygenic risk scores have not been well studied. Here, the authors have developed polygenic risk scores for 16 cancers in two large cohorts and identified positive and inverse cross-cancer associations.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
4.6
作者：
Cheng TH;Thompson D;Painter J;O'Mara T;Gorman M;Martin L;Palles C;Jones A;Buchanan DD;Win AK;Hopper J;Jenkins M;Lindor NM;Newcomb PA;Gallinger S;Conti D;Schumacher F;Casey G;Giles GG;Pharoah P;Peto J;Cox A;Swerdlow A;Couch F;Cunningham JM;Goode EL;Winham SJ;Lambrechts D;Fasching P;Burwinkel B;Brenner H;Brauch H;Chang-Claude J;Salvesen HB;Kristensen V;Darabi H;Li J;Liu T;Lindblom A;Hall P;de Polanco ME;Sans M;Carracedo A;Castellvi-Bel S;Rojas-Martinez A;Aguiar Jnr S;Teixeira MR;Dunning AM;Dennis J;Otton G;Proietto T;Holliday E;Attia J;Ashton K;Scott RJ;McEvoy M;Dowdy SC;Fridley BL;Werner HM;Trovik J;Njolstad TS;Tham E;Mints M;Runnebaum I;Hillemanns P;Dörk T;Amant F;Schrauwen S;Hein A;Beckmann MW;Ekici A;Czene K;Meindl A;Bolla MK;Michailidou K;Tyrer JP;Wang Q;Ahmed S;Healey CS;Shah M;Annibali D;Depreeuw J;Al-Tassan NA;Harris R;Meyer BF;Whiffin N;Hosking FJ;Kinnersley B;Farrington SM;Timofeeva M;Tenesa A;Campbell H;Haile RW;Hodgson S;Carvajal-Carmona L;Cheadle JP;Easton D;Dunlop M;Houlston R;Spurdle A;Tomlinson I
通讯作者：
Tomlinson I
影响因子：
11.2
作者：
Fehringer G;Kraft P;Pharoah PD;Eeles RA;Chatterjee N;Schumacher FR;Schildkraut JM;Lindström S;Brennan P;Bickeböller H;Houlston RS;Landi MT;Caporaso N;Risch A;Amin Al Olama A;Berndt SI;Giovannucci EL;Grönberg H;Kote-Jarai Z;Ma J;Muir K;Stampfer MJ;Stevens VL;Wiklund F;Willett WC;Goode EL;Permuth JB;Risch HA;Reid BM;Bezieau S;Brenner H;Chan AT;Chang-Claude J;Hudson TJ;Kocarnik JK;Newcomb PA;Schoen RE;Slattery ML;White E;Adank MA;Ahsan H;Aittomäki K;Baglietto L;Blomquist C;Canzian F;Czene K;Dos-Santos-Silva I;Eliassen AH;Figueroa JD;Flesch-Janys D;Fletcher O;Garcia-Closas M;Gaudet MM;Johnson N;Hall P;Hazra A;Hein R;Hofman A;Hopper JL;Irwanto A;Johansson M;Kaaks R;Kibriya MG;Lichtner P;Liu J;Lund E;Makalic E;Meindl A;Müller-Myhsok B;Muranen TA;Nevanlinna H;Peeters PH;Peto J;Prentice RL;Rahman N;Sanchez MJ;Schmidt DF;Schmutzler RK;Southey MC;Tamimi R;Travis RC;Turnbull C;Uitterlinden AG;Wang Z;Whittemore AS;Yang XR;Zheng W;Buchanan DD;Casey G;Conti DV;Edlund CK;Gallinger S;Haile RW;Jenkins M;Le Marchand L;Li L;Lindor NM;Schmit SL;Thibodeau SN;Woods MO;Rafnar T;Gudmundsson J;Stacey SN;Stefansson K;Sulem P;Chen YA;Tyrer JP;Christiani DC;Wei Y;Shen H;Hu Z;Shu XO;Shiraishi K;Takahashi A;Bossé Y;Obeidat M;Nickle D;Timens W;Freedman ML;Li Q;Seminara D;Chanock SJ;Gong J;Peters U;Gruber SB;Amos CI;Sellers TA;Easton DF;Hunter DJ;Haiman CA;Henderson BE;Hung RJ;Ovarian Cancer Association Consortium (OCAC);PRACTICAL Consortium;Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON);Colorectal Transdisciplinary (CORECT) Study;African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
通讯作者：
African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
8q24 基因沙漠：非编码转录活性的绿洲。
影响因子：
3.7
作者：
Huppi K;Pitt JJ;Wahlberg BM;Caplen NJ
通讯作者：
Caplen NJ
影响因子：
3.5
作者：
Gaspar TB;Sá A;Lopes JM;Sobrinho-Simões M;Soares P;Vinagre J
通讯作者：
Vinagre J