Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
Huang, Joyce Y.; Larose, Tricia L.; Luu, Hung N.; Wang, Renwei; Fanidi, Anouar; Alcala, Karine; Stevens, Victoria L.; Weinstein, Stephanie J.; Albanes, Demetrius; Caporaso, Neil E.; Purdue, Mark P.; Ziegler, Regina G.; Freedman, Neal D.; Lan, Qing; Prentice, Ross L.; Pettinger, Mary; Thomson, Cynthia A.; Cai, Qiuyin; Wu, Jie; Blot, William J.; Shu, Xiao-Ou; Zheng, Wei; Arslan, Alan A.; Zeleniuch-Jacquotte, Anne; Le Marchand, Loic; Wilkens, Lynn R.; Haiman, Christopher A.; Zhang, Xuehong; Stampfer, Meir J.; Giles, Graham G.; Hodge, Allison M.; Severi, Gianluca; Johansson, Mikael; Grankvist, Kjell; Langhammer, Arnulf; Hveem, Kristian; Xiang, Yong-Bing; Li, Hong-Lan; Gao, Yu-Tang; Visvanathan, Kala; Ueland, Per M.; Midttun, Oivind; Ulvi, Arve; Buring, Julie E.; Lee, I-Min; SeSS, Howard D.; Gaziano, J. Michael; Manjer, Jonas; Relton, Caroline; Koh, Woon-Puay; Brennan, Paul; Johansson, Mattias; Yuan, Jian-Min; Han, Jiali
ISI:000477508300001
ISSN: 0020-7136
CID: 4028282
Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
Johnson, Catherine Owens; Minh Nguyen; Roth, Gregory A.; Nichols, Emma; Alam, Tahiya; Abate, Degu; Abd-Allah, Foad; Abdelalim, Ahmed; Abraha, Haftom Niguse; Abu-Rmeileh, Niveen Me; Adebayo, Oladimeji M.; Adeoye, Abiodun Moshood; Agarwal, Gina; Agrawal, Sutapa; Aichour, Amani Nidhal; Aichour, Ibtihel; Aichour, Miloud Taki Eddine; Alahdab, Fares; Ali, Raghib; Alvis-Guzman, Nelson; Anber, Nahla Hamed; Anjomshoa, Mina; Arabloo, Jalal; Arauz, Antonio; Arnlov, Johan; Arora, Amit; Awasthi, Ashish; Banach, Maciej; Barboza, Miguel A.; Barker-Collo, Suzanne Lyn; Barnighausen, Till Winfried; Basu, Sanjay; Belachew, Abate Bekele; Belayneh, Yaschilal Muche; Bennett, Derrick A.; Bensenor, Isabela M.; Bhattacharyya, Krittika; Biadgo, Belete; Bijani, Ali; Bikbov, Boris; Bin Sayeed, Muhammad Shahdaat; Butt, Zahid A.; Cahuana-Hurtado, Lucero; Carrero, Juan J.; Carvalho, Felix; Castaneda-Orjuela, Carlos A.; Castro, Franz; Catala-Lopez, Ferran; Chaiah, Yazan; Chiang, Peggy Pei-Chia; Choi, Jee-Young J.; Christensen, Hanne; Chu, Dinh-Toi; Cortinovis, Monica; Moura Damasceno, Albertino Antonio; Dandona, Lalit; Dandona, Rakhi; Daryani, Ahmad; Davletov, Kairat; De Courten, Barbora; De la Cruz-Gongora, Vanessa; Degefa, Meaza Girma; Dharmaratne, Samath Dhamminda; Diaz, Daniel; Dubey, Manisha; Duken, Eyasu Ejeta; Edessa, Dumessa; Endres, Matthias; Faraon, Emerito Jose A.; Farzadfar, Farshad; Fernandes, Eduarda; Fischer, Florian; Flor, Luisa Sorio; Ganji, Morsaleh; Gebre, Abadi Kahsu; Gebremichael, Teklu Gebrehiwo; Geta, Birhanu; Gezae, Kebede Embaye; Gill, Paramjit Singh; Gnedovskaya, Elena V.; Gomez-Dantes, Hector; Goulart, Alessandra C.; Grosso, Giuseppe; Guo, Yuming; Gupta, Rajeev; Haj-Mirzaian, Arvin; Haj-Mirzaian, Arya; Hamidi, Samer; Hankey, Graeme J.; Hassen, Hamid Yimam; Hay, Simon I.; Hegazy, Mohamed I.; Heidari, Behnam; Herial, Nabeel A.; Hosseini, Mohammad Ali; Hostiuc, Sorin; Irvani, Seyed Sina Naghibi; Islam, Sheikh Mohammed Shariful; Jahanmehr, Nader; Javanbakht, Mehdi; Jha, Ravi Prakash; Jonas, Jost B.; Jozwiak, Jacek Jerzy; Jurisson, Mikk; Kahsay, Amaha; Kalani, Rizwan; Kalkonde, Yogeshwar; Kamil, Teshome Abegaz; Kanchan, Tanuj; Karch, Andre; Karimi, Narges; Karimi-Sari, Hamidreza; Kasaeian, Amir; Kassa, Tesfaye Dessale; Kazemeini, Hossein; Kefale, Adane Teshome; Khader, Yousef Saleh; Khalil, Ibrahim A.; Khan, Ejaz Ahmad; Khang, Young-Ho; Khubchandani, Jagdish; Kim, Daniel; Kim, Yun Jin; Kisa, Adnan; Kivimaki, Mika; Koyanagi, Ai; Krishnamurthi, Rita K.; Kumar, G. Anil; Lafranconi, Alessandra; Lewington, Sarah; Li, Shanshan; Lo, Warren David; Lopez, Alan D.; Lorkowski, Stefan; Lotufo, Paulo A.; Mackay, Mark T.; Majdan, Marek; Majdzadeh, Reza; Majeed, Azeem; Malekzadeh, Reza; Manafi, Navid; Mansournia, Mohammad Ali; Mehndiratta, Man Mohan; Mehta, Varshil; Mengistu, Getnet; Meretoja, Atte; Meretoja, Tuomo J.; Miazgowski, Bartosz; Miazgowski, Tomasz; Miller, Ted R.; Mirrakhimov, Erkin M.; Mohajer, Bahram; Mohammad, Yousef; Mohammadoo-Khorasani, Milad; Mohammed, Shafiu; Mohebi, Farnam; Mokdad, Ali H.; Mokhayeri, Yaser; Moradi, Ghobad; Morawska, Lidia; Velasquez, Ilais Moreno; Mousavi, Seyyed Meysam; Muhammed, Oumer Sada S.; Muruet, Walter; Naderi, Mehdi; Naghavi, Mohsen; Naik, Gurudatta; Nascimento, Bruno Ramos; Negoi, Ruxandra Irina; Cuong Tat Nguyen; Long Hoang Nguyen; Nirayo, Yirga Legesse; Norrving, Bo; Noubiap, Jean Jacques; Ofori-Asenso, Richard; Ogbo, Felix Akpojene; Olagunju, Andrew T.; Olagunju, Tinuke O.; Owolabi, Mayowa Ojo; Pandian, Jeyaraj Durai; Patel, Shanti; Perico, Norberto; Piradov, Michael A.; Polinder, Suzanne; Postma, Maarten J.; Poustchi, Hossein; Prakash, V.; Qorbani, Mostafa; Rafiei, Alireza; Rahim, Fakher; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Mahfuzar; Rahman, Muhammad Aziz; Reis, Cesar; Remuzzi, Giuseppe; Renzaho, Andre M. N.; Ricci, Stefano; Roberts, Nicholas L. S.; Robinson, Stephen R.; Roever, Leonardo; Roshandel, Gholamreza; Sabbagh, Parisa; Safari, Hosein; Safari, Saeed; Safiri, Saeid; Sahebkar, Amirhossein; Zahabi, Saleh Salehi; Samy, Abdallah M.; Santalucia, Paola; Santos, Itamar S.; Santos, Joao Vasco; Milicevic, Milena M. Santric; Sartorius, Benn; Sawant, Arundhati R.; Schutte, Aletta Elisabeth; Sepanlou, Sadaf G.; Shafieesabet, Azadeh; Shaikh, Masood Ali; Shams-Beyranvand, Mehran; Sheikh, Aziz; Sheth, Kevin N.; Shibuya, Kenji; Shigematsu, Mika; Shin, Min-Jeong; Shiue, Ivy; Siabani, Soraya; Sobaih, Badr Hasan; Sposato, Luciano A.; Sutradhar, Ipsita; Sylaja, P. A.; Szoeke, Cassandra E. I.; Ao, Braden James Te; Temsah, Mohamad-Hani; Temsah, Omar; Thrift, Amanda G.; Tonelli, Marcello; Topor-Madry, Roman; Bach Xuan Tran; Khanh Bao Tran; Truelsen, Thomas Clement; Tsadik, Afewerki Gebremeskel; Ullah, Irfan; Uthman, Olalekan A.; Vaduganathan, Muthiah; Valdez, Pascual R.; Vasankari, Tommi Juhani; Vasanthan, Rajagopalan; Venketasubramanian, Narayanaswamy; Vosoughi, Kia; Giang Thu Vu; Waheed, Yasir; Weiderpass, Elisabete; Weldegwergs, Kidu Gidey; Westerman, Ronny; Wolfe, Charles D. A.; Wondafrash, Dawit Zewdu; Xu, Gelin; Yadollahpour, Ali; Yamada, Tomohide; Yatsuya, Hiroshi; Yimer, Ebrahim M.; Yonemoto, Naohiro; Yousefifard, Mahmoud; Yu, Chuanhua; Zaidi, Zoubida; Zamani, Mohammad; Zarghi, Afshin; Zhang, Yunquan; Zodpey, Sanjay; Feigin, Valery L.; Vos, Theo; Murray, Christopher J. L.
ISI:000464140400013
ISSN: 1474-4422
CID: 4703032
Germline genetic variation affects the immune response in cancer [Meeting Abstract]
Sayaman, R; Saad, M; Thorsson, V; Mokrab, Y; Hendrickx, W; Farshidfar, F; Kirchhoff, T; Sweis, R; Syed, N; Bathe, O; Porta-Pardo, E; Stretch, C; Hu, D; Huntsman, S; Roelands, Master J; Shelley, S; Wolf, D; Galon, J; Marincola, F; Ceccarelli, M; Ziv, E; Bedognetti, D
Background Somatic genetic alterations have been associated with differential disposition of the intratumoral immune milieu. In contrast, the role of germline genetics remains largely unknown. The Cancer Genome Atlas (TCGA) Pan-Cancer Immune Response Working Group recently analyzed associations between immunological features of tumor microenvironment, prognosis, and tumor-intrinsic properties (including somatic mutations and copy number aberrations). The study generated a comprehensive set of per-sample immune response signatures, and identified distinct tumor immunological subtypes shared across multiple cancer types [1]. Here, we examined the germline genetic contribution to >100 such immune response signatures, considered as potential traits, in >9,000 study participants across 30 different cancer types in the TCGA. Methods We used SNP data from Affymetrix 6.0 arrays typed on normal tissue and blood. After stringent quality control, we imputed missing SNPs using the Haplotype Reference Consortium dataset and included SNPs with minor allele frequency >0.005 and imputation quality R2>0.5. We inferred genetic ancestry using principal components analysis. We estimated genome-wide heritability of the immune signatures using the genomic-relatedness-based restricted maximumlikelihood (GREML) approach implemented in genome-wide complex trait analysis (GCTA). We performed genome-wide association studies (GWAS) using linear regression models. All analyses were adjusted for cancer type, age at diagnosis, gender, and genetic ancestry using principal components 1-7. Linear regression was also applied to germline exome sequence data [2] to evaluate rare variant associations. Results Across different tumor types, we found significant heritability (FDR< 0.05) for estimates of innate and adaptive immune cell enrichment including natural killer cells, activated dendritic cells, eosinophils and neutrophils, and T-cell subsets (CD8 Cytotoxic, T-helper, T-follicular helper, T-effector memory, T-central memory, Th1 and Th17 cells) respectively, as well as for antigen-presenting machinery and interferon-related signatures. Furthermore, we found significant interactions between germline modifiers and distinct immune subtypes (FDR<0.05). Through GWAS analysis, we identified several polymorphisms associated with both immune cells and immunomodulatory signaling passing the genome-wide significance threshold (p<5E-8). Two SNPs previously associated with the risk of several auto-immune diseases [3], rs2111485 and rs1990760 mapping to Interferon Induced Helicase C Domain 1 (IFIH1) locus, were significantly correlated with interferon signaling in tumors (Figure 1). Moreover, suggestive associations between rare variants and immune response traits were found. Conclusions We demonstrated that intratumoral immune disposition is partially under germline control through systematic pan-cancer analysis. Germline variants associated with differential immune response might be used to stratify patients based on likelihood of treatment response and to prioritize targets for development of novel therapies. (Figure Preseted)
EMBASE:629905729
ISSN: 2051-1426
CID: 4226632