Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers.
Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers.
复制标题
常见癌症中与肿瘤免疫浸润相关的多基因风险评分。
作者：
多基因风险评分（PRS）已被用来预测患癌症的风险。然而，PRS 是否与实体瘤中的免疫浸润相关仍不清楚。我们利用之前全基因组关联研究中发现的风险变异构建了乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌和前列腺癌等常见癌症的 PRS，并全面评估了它们与之前从癌症基因组图谱中估计的 139 种免疫特征的关联。我们在名义显着性 (p < 0.05) 水平上确定了 PRS 与免疫特征之间的 31 种显着关联。在按乳腺癌、结直肠癌、肺腺癌和肺鳞状细胞癌分期分层的分析中，我们发现了 65 个显着关联，其中包括总体分析未检测到的 56 个关联。我们的研究结果为遗传易感性在癌症发展、预后的免疫反应中的作用以及早期诊断或治疗靶向策略的潜在作用提供了新的见解。目前尚不清楚遗传易感性是否有助于常见癌症的肿瘤免疫浸润。我们系统地研究了常见癌症中多基因风险评分（PRS）与肿瘤免疫浸润之间的关联。首先，我们利用之前全基因组关联研究中确定的风险变异构建了常见癌症的 PRS。然后，我们通过检查癌症基因组图谱 (TCGA) 中肿瘤组织的基因表达数据，分析了先前研究预测的 139 种免疫特征。我们应用回归分析来总体评估 PRS 与每种癌症免疫特征之间的关联，并按阶段分层，其中包括 2160 例经病理证实的白人乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌和前列腺癌病例。在名义上 (p < 0.05) 显着性水平上，我们确定了 PRS 与免疫特征之间的 31 个显着关联。在对乳腺癌、结直肠癌、肺腺癌和肺鳞状细胞癌按阶段分层的分析中，我们发现了 65 个显着关联，其中包括总体分析未检测到的 56 个关联。这项研究为影响免疫浸润的遗传风险因素提供了证据，并为遗传易感性在免疫反应、潜在癌症发展、预后以及早期诊断或治疗靶向策略的潜在作用中的作用提供了新的见解。
Polygenic risk scores (PRSs) have been used to predict the risk of developing cancer. However, whether PRSs are associated with immune infiltration in solid tumors remains unclear. We constructed PRSs for common cancers of the breast, colorectum, lung, ovary, pancreas, and prostate using risk variants identified in previous genome-wide association studies, and comprehensively evaluated their associations with 139 immune traits previously estimated from The Cancer Genome Atlas. We identified 31 significant associations between PRSs and immune traits at a nominal (p < 0.05) level of significance. In the analyses stratified by stage for breast cancer, colorectal cancer, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. Our findings provide novel insights into the role of genetic susceptibility in the immune responses underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy. It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.
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影响因子：
3.9
作者：
Ben-Ali, Meriem;Corre, Beatrice;Quintana-Murci, Lluis
通讯作者：
Quintana-Murci, Lluis
影响因子：
64.8
作者：
Michailidou K;Lindström S;Dennis J;Beesley J;Hui S;Kar S;Lemaçon A;Soucy P;Glubb D;Rostamianfar A;Bolla MK;Wang Q;Tyrer J;Dicks E;Lee A;Wang Z;Allen J;Keeman R;Eilber U;French JD;Qing Chen X;Fachal L;McCue K;McCart Reed AE;Ghoussaini M;Carroll JS;Jiang X;Finucane H;Adams M;Adank MA;Ahsan H;Aittomäki K;Anton-Culver H;Antonenkova NN;Arndt V;Aronson KJ;Arun B;Auer PL;Bacot F;Barrdahl M;Baynes C;Beckmann MW;Behrens S;Benitez J;Bermisheva M;Bernstein L;Blomqvist C;Bogdanova NV;Bojesen SE;Bonanni B;Børresen-Dale AL;Brand JS;Brauch H;Brennan P;Brenner H;Brinton L;Broberg P;Brock IW;Broeks A;Brooks-Wilson A;Brucker SY;Brüning T;Burwinkel B;Butterbach K;Cai Q;Cai H;Caldés T;Canzian F;Carracedo A;Carter BD;Castelao JE;Chan TL;David Cheng TY;Seng Chia K;Choi JY;Christiansen H;Clarke CL;NBCS Collaborators;Collée M;Conroy DM;Cordina-Duverger E;Cornelissen S;Cox DG;Cox A;Cross SS;Cunningham JM;Czene K;Daly MB;Devilee P;Doheny KF;Dörk T;Dos-Santos-Silva I;Dumont M;Durcan L;Dwek M;Eccles DM;Ekici AB;Eliassen AH;Ellberg C;Elvira M;Engel C;Eriksson M;Fasching PA;Figueroa J;Flesch-Janys D;Fletcher O;Flyger H;Fritschi L;Gaborieau V;Gabrielson M;Gago-Dominguez M;Gao YT;Gapstur SM;García-Sáenz JA;Gaudet MM;Georgoulias V;Giles GG;Glendon G;Goldberg MS;Goldgar DE;González-Neira A;Grenaker Alnæs GI;Grip M;Gronwald J;Grundy A;Guénel P;Haeberle L;Hahnen E;Haiman CA;Håkansson N;Hamann U;Hamel N;Hankinson S;Harrington P;Hart SN;Hartikainen JM;Hartman M;Hein A;Heyworth J;Hicks B;Hillemanns P;Ho DN;Hollestelle A;Hooning MJ;Hoover RN;Hopper JL;Hou MF;Hsiung CN;Huang G;Humphreys K;Ishiguro J;Ito H;Iwasaki M;Iwata H;Jakubowska A;Janni W;John EM;Johnson N;Jones K;Jones M;Jukkola-Vuorinen A;Kaaks R;Kabisch M;Kaczmarek K;Kang D;Kasuga Y;Kerin MJ;Khan S;Khusnutdinova E;Kiiski JI;Kim SW;Knight JA;Kosma VM;Kristensen VN;Krüger U;Kwong A;Lambrechts D;Le Marchand L;Lee E;Lee MH;Lee JW;Neng Lee C;Lejbkowicz F;Li J;Lilyquist J;Lindblom A;Lissowska J;Lo WY;Loibl S;Long J;Lophatananon A;Lubinski J;Luccarini C;Lux MP;Ma ESK;MacInnis RJ;Maishman T;Makalic E;Malone KE;Kostovska IM;Mannermaa A;Manoukian S;Manson JE;Margolin S;Mariapun S;Martinez ME;Matsuo K;Mavroudis D;McKay J;McLean C;Meijers-Heijboer H;Meindl A;Menéndez P;Menon U;Meyer J;Miao H;Miller N;Taib NAM;Muir K;Mulligan AM;Mulot C;Neuhausen SL;Nevanlinna H;Neven P;Nielsen SF;Noh DY;Nordestgaard BG;Norman A;Olopade OI;Olson JE;Olsson H;Olswold C;Orr N;Pankratz VS;Park SK;Park-Simon TW;Lloyd R;Perez JIA;Peterlongo P;Peto J;Phillips KA;Pinchev M;Plaseska-Karanfilska D;Prentice R;Presneau N;Prokofyeva D;Pugh E;Pylkäs K;Rack B;Radice P;Rahman N;Rennert G;Rennert HS;Rhenius V;Romero A;Romm J;Ruddy KJ;Rüdiger T;Rudolph A;Ruebner M;Rutgers EJT;Saloustros E;Sandler DP;Sangrajrang S;Sawyer EJ;Schmidt DF;Schmutzler RK;Schneeweiss A;Schoemaker MJ;Schumacher F;Schürmann P;Scott RJ;Scott C;Seal S;Seynaeve C;Shah M;Sharma P;Shen CY;Sheng G;Sherman ME;Shrubsole MJ;Shu XO;Smeets A;Sohn C;Southey MC;Spinelli JJ;Stegmaier C;Stewart-Brown S;Stone J;Stram DO;Surowy H;Swerdlow A;Tamimi R;Taylor JA;Tengström M;Teo SH;Beth Terry M;Tessier DC;Thanasitthichai S;Thöne K;Tollenaar RAEM;Tomlinson I;Tong L;Torres D;Truong T;Tseng CC;Tsugane S;Ulmer HU;Ursin G;Untch M;Vachon C;van Asperen CJ;Van Den Berg D;van den Ouweland AMW;van der Kolk L;van der Luijt RB;Vincent D;Vollenweider J;Waisfisz Q;Wang-Gohrke S;Weinberg CR;Wendt C;Whittemore AS;Wildiers H;Willett W;Winqvist R;Wolk A;Wu AH;Xia L;Yamaji T;Yang XR;Har Yip C;Yoo KY;Yu JC;Zheng W;Zheng Y;Zhu B;Ziogas A;Ziv E;ABCTB Investigators;ConFab/AOCS Investigators;Lakhani SR;Antoniou AC;Droit A;Andrulis IL;Amos CI;Couch FJ;Pharoah PDP;Chang-Claude J;Hall P;Hunter DJ;Milne RL;García-Closas M;Schmidt MK;Chanock SJ;Dunning AM;Edwards SL;Bader GD;Chenevix-Trench G;Simard J;Kraft P;Easton DF
通讯作者：
Easton DF
影响因子：
16.6
作者：
Cortes-Ciriano I;Lee S;Park WY;Kim TM;Park PJ
通讯作者：
Park PJ
影响因子：
4.7
作者：
Bao, Xuanwen;Shi, Run;Wang, Yanfang
通讯作者：
Wang, Yanfang
跨务基因组全基因组关联的前列腺癌荟萃分析确定了新的敏感性基因座并告知遗传风险预测。
影响因子：
30.8
作者：
Conti DV;Darst BF;Moss LC;Saunders EJ;Sheng X;Chou A;Schumacher FR;Olama AAA;Benlloch S;Dadaev T;Brook MN;Sahimi A;Hoffmann TJ;Takahashi A;Matsuda K;Momozawa Y;Fujita M;Muir K;Lophatananon A;Wan P;Le Marchand L;Wilkens LR;Stevens VL;Gapstur SM;Carter BD;Schleutker J;Tammela TLJ;Sipeky C;Auvinen A;Giles GG;Southey MC;MacInnis RJ;Cybulski C;Wokołorczyk D;Lubiński J;Neal DE;Donovan JL;Hamdy FC;Martin RM;Nordestgaard BG;Nielsen SF;Weischer M;Bojesen SE;Røder MA;Iversen P;Batra J;Chambers S;Moya L;Horvath L;Clements JA;Tilley W;Risbridger GP;Gronberg H;Aly M;Szulkin R;Eklund M;Nordström T;Pashayan N;Dunning AM;Ghoussaini M;Travis RC;Key TJ;Riboli E;Park JY;Sellers TA;Lin HY;Albanes D;Weinstein SJ;Mucci LA;Giovannucci E;Lindstrom S;Kraft P;Hunter DJ;Penney KL;Turman C;Tangen CM;Goodman PJ;Thompson IM Jr;Hamilton RJ;Fleshner NE;Finelli A;Parent MÉ;Stanford JL;Ostrander EA;Geybels MS;Koutros S;Freeman LEB;Stampfer M;Wolk A;Håkansson N;Andriole GL;Hoover RN;Machiela MJ;Sørensen KD;Borre M;Blot WJ;Zheng W;Yeboah ED;Mensah JE;Lu YJ;Zhang HW;Feng N;Mao X;Wu Y;Zhao SC;Sun Z;Thibodeau SN;McDonnell SK;Schaid DJ;West CML;Burnet N;Barnett G;Maier C;Schnoeller T;Luedeke M;Kibel AS;Drake BF;Cussenot O;Cancel-Tassin G;Menegaux F;Truong T;Koudou YA;John EM;Grindedal EM;Maehle L;Khaw KT;Ingles SA;Stern MC;Vega A;Gómez-Caamaño A;Fachal L;Rosenstein BS;Kerns SL;Ostrer H;Teixeira MR;Paulo P;Brandão A;Watya S;Lubwama A;Bensen JT;Fontham ETH;Mohler J;Taylor JA;Kogevinas M;Llorca J;Castaño-Vinyals G;Cannon-Albright L;Teerlink CC;Huff CD;Strom SS;Multigner L;Blanchet P;Brureau L;Kaneva R;Slavov C;Mitev V;Leach RJ;Weaver B;Brenner H;Cuk K;Holleczek B;Saum KU;Klein EA;Hsing AW;Kittles RA;Murphy AB;Logothetis CJ;Kim J;Neuhausen SL;Steele L;Ding YC;Isaacs WB;Nemesure B;Hennis AJM;Carpten J;Pandha H;Michael A;De Ruyck K;De Meerleer G;Ost P;Xu J;Razack A;Lim J;Teo SH;Newcomb LF;Lin DW;Fowke JH;Neslund-Dudas C;Rybicki BA;Gamulin M;Lessel D;Kulis T;Usmani N;Singhal S;Parliament M;Claessens F;Joniau S;Van den Broeck T;Gago-Dominguez M;Castelao JE;Martinez ME;Larkin S;Townsend PA;Aukim-Hastie C;Bush WS;Aldrich MC;Crawford DC;Srivastava S;Cullen JC;Petrovics G;Casey G;Roobol MJ;Jenster G;van Schaik RHN;Hu JJ;Sanderson M;Varma R;McKean-Cowdin R;Torres M;Mancuso N;Berndt SI;Van Den Eeden SK;Easton DF;Chanock SJ;Cook MB;Wiklund F;Nakagawa H;Witte JS;Eeles RA;Kote-Jarai Z;Haiman CA
通讯作者：
Haiman CA