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  1. Article ; Online: Publisher correction: Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.

    Fang, Jun / Jia, Jinping / Makowski, Matthew / Xu, Mai / Wang, Zhaoming / Zhang, Tongwu / Hoskins, Jason W / Choi, Jiyeon / Han, Younghun / Zhang, Mingfeng / Thomas, Janelle / Kovacs, Michael / Collins, Irene / Dzyadyk, Marta / Thompson, Abbey / O'Neill, Maura / Das, Sudipto / Lan, Qi / Koster, Roelof /
    Stolzenberg-Solomon, Rachael S / Kraft, Peter / Wolpin, Brian M / Jansen, Pascal W T C / Olson, Sara / McGlynn, Katherine A / Kanetsky, Peter A / Chatterjee, Nilanjan / Barrett, Jennifer H / Dunning, Alison M / Taylor, John C / Newton-Bishop, Julia A / Timothy Bishop, D / Andresson, Thorkell / Petersen, Gloria M / Amos, Christopher I / Iles, Mark M / Nathanson, Katherine L / Teresa Landi, Maria / Vermeulen, Michiel / Brown, Kevin M / Amundadottir, Laufey T

    Nature communications

    2018  Volume 9, Page(s) 16159

    Abstract: This corrects the article DOI: 10.1038/ncomms15034. ...

    Abstract This corrects the article DOI: 10.1038/ncomms15034.
    Language English
    Publishing date 2018-03-05
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms16159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.

    Fang, Jun / Jia, Jinping / Makowski, Matthew / Xu, Mai / Wang, Zhaoming / Zhang, Tongwu / Hoskins, Jason W / Choi, Jiyeon / Han, Younghun / Zhang, Mingfeng / Thomas, Janelle / Kovacs, Michael / Collins, Irene / Dzyadyk, Marta / Thompson, Abbey / O'Neill, Maura / Das, Sudipto / Lan, Qi / Koster, Roelof /
    Stolzenberg-Solomon, Rachael S / Kraft, Peter / Wolpin, Brian M / Jansen, Pascal W T C / Olson, Sara / McGlynn, Katherine A / Kanetsky, Peter A / Chatterjee, Nilanjan / Barrett, Jennifer H / Dunning, Alison M / Taylor, John C / Newton-Bishop, Julia A / Bishop, D Timothy / Andresson, Thorkell / Petersen, Gloria M / Amos, Christopher I / Iles, Mark M / Nathanson, Katherine L / Landi, Maria Teresa / Vermeulen, Michiel / Brown, Kevin M / Amundadottir, Laufey T

    Nature communications

    2017  Volume 8, Page(s) 15034

    Abstract: Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal ... ...

    Abstract Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
    MeSH term(s) Alleles ; Cell Line, Tumor ; Chromosome Mapping ; Chromosomes, Human, Pair 5 ; DNA-Binding Proteins/antagonists & inhibitors ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Histones/genetics ; Histones/metabolism ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; Melanoma/genetics ; Melanoma/metabolism ; Melanoma/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Polymorphism, Single Nucleotide ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; Skin Neoplasms/genetics ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Telomerase/antagonists & inhibitors ; Telomerase/genetics ; Telomerase/metabolism ; Telomere Homeostasis ; Testicular Neoplasms/genetics ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/pathology ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances DNA-Binding Proteins ; Histones ; RNA, Small Interfering ; Transcription Factors ; ZNF148 protein, human ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2017-05-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms15034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

    Zhang, Mingfeng / Wang, Zhaoming / Obazee, Ofure / Jia, Jinping / Childs, Erica J / Hoskins, Jason / Figlioli, Gisella / Mocci, Evelina / Collins, Irene / Chung, Charles C / Hautman, Christopher / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E /
    Goodman, Phyllis J / Kamineni, Aruna / Kolonel, Laurence N / Kulke, Matthew H / Malats, Núria / Olson, Sara H / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Brais, Lauren / Bueno-de-Mesquita, H Bas / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Bijlsma, Maarten F / Brenner, Hermann / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Cavestro, Giulia Martina / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Boggi, Ugo / Gaziano, J Michael / Gazouli, Maria / Giovannucci, Edward L / Goggins, Michael / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Hu, Nan / Hunter, David J / Iskierka-Jazdzewska, Elzbieta / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Neale, Rachel E / Oberg, Ann L / Panico, Salvatore / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Purdue, Mark / Quiros, J Ramón / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Scelo, Ghislaine / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Strobel, Oliver / Sund, Malin / Małecka-Panas, Ewa / Taylor, Philip R / Tavano, Francesca / Travis, Ruth C / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vashist, Yogesh / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Kooperberg, Charles / Risch, Harvey A / Jacobs, Eric J / Li, Donghui / Fuchs, Charles / Hoover, Robert / Hartge, Patricia / Chanock, Stephen J / Petersen, Gloria M / Stolzenberg-Solomon, Rachael S / Wolpin, Brian M / Kraft, Peter / Klein, Alison P / Canzian, Federico / Amundadottir, Laufey T

    Oncotarget

    2016  Volume 7, Issue 41, Page(s) 66328–66343

    Abstract: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes ( ... ...

    Abstract Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
    MeSH term(s) Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 5/genetics ; Chromosomes, Human, Pair 8/genetics ; Datasets as Topic ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Genotype ; Humans ; Pancreatic Neoplasms/genetics ; Polymorphism, Single Nucleotide/genetics
    Language English
    Publishing date 2016-08-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.11041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.

    Wolpin, Brian M / Rizzato, Cosmeri / Kraft, Peter / Kooperberg, Charles / Petersen, Gloria M / Wang, Zhaoming / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Canzian, Federico / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Jacobs, Eric J / Kamineni, Aruna / Klein, Alison P /
    Kolonel, Laurence N / Kulke, Matthew H / Li, Donghui / Malats, Núria / Olson, Sara H / Risch, Harvey A / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Austin, Melissa A / Barfield, Richard / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Brotzman, Michelle / Büchler, Markus W / Bueno-de-Mesquita, H Bas / Bugert, Peter / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Chung, Charles / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Funel, Niccola / Gaziano, J Michael / Giese, Nathalia A / Giovannucci, Edward L / Goggins, Michael / Gorman, Megan J / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Henderson, Brian E / Holly, Elizabeth A / Hu, Nan / Hunter, David J / Innocenti, Federico / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / LaCroix, Andrea / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Nakamura, Yusuke / Oberg, Ann L / Owzar, Kouros / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Piepoli, Ada / Porta, Miquel / Real, Francisco X / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Taylor, Philip R / Theodoropoulos, George E / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Wu, Chen / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Hoover, Robert / Hartge, Patricia / Fuchs, Charles / Chanock, Stephen J / Stolzenberg-Solomon, Rachael S / Amundadottir, Laufey T

    Nature genetics

    2014  Volume 46, Issue 9, Page(s) 994–1000

    Abstract: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) ...

    Abstract We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
    MeSH term(s) Aged ; Case-Control Studies ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Genotype ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/genetics ; Polymorphism, Single Nucleotide/genetics ; White People/genetics
    Language English
    Publishing date 2014-08-03
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

    Sampson, Joshua N / Wheeler, William A / Yeager, Meredith / Panagiotou, Orestis / Wang, Zhaoming / Berndt, Sonja I / Lan, Qing / Abnet, Christian C / Amundadottir, Laufey T / Figueroa, Jonine D / Landi, Maria Teresa / Mirabello, Lisa / Savage, Sharon A / Taylor, Philip R / De Vivo, Immaculata / McGlynn, Katherine A / Purdue, Mark P / Rajaraman, Preetha / Adami, Hans-Olov /
    Ahlbom, Anders / Albanes, Demetrius / Amary, Maria Fernanda / An, She-Juan / Andersson, Ulrika / Andriole, Gerald / Andrulis, Irene L / Angelucci, Emanuele / Ansell, Stephen M / Arici, Cecilia / Armstrong, Bruce K / Arslan, Alan A / Austin, Melissa A / Baris, Dalsu / Barkauskas, Donald A / Bassig, Bryan A / Becker, Nikolaus / Benavente, Yolanda / Benhamou, Simone / Berg, Christine / Van Den Berg, David / Bernstein, Leslie / Bertrand, Kimberly A / Birmann, Brenda M / Black, Amanda / Boeing, Heiner / Boffetta, Paolo / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Brinton, Louise / Brooks-Wilson, Angela R / Bueno-de-Mesquita, H Bas / Burdett, Laurie / Buring, Julie / Butler, Mary Ann / Cai, Qiuyin / Cancel-Tassin, Geraldine / Canzian, Federico / Carrato, Alfredo / Carreon, Tania / Carta, Angela / Chan, John K C / Chang, Ellen T / Chang, Gee-Chen / Chang, I-Shou / Chang, Jiang / Chang-Claude, Jenny / Chen, Chien-Jen / Chen, Chih-Yi / Chen, Chu / Chen, Chung-Hsing / Chen, Constance / Chen, Hongyan / Chen, Kexin / Chen, Kuan-Yu / Chen, Kun-Chieh / Chen, Ying / Chen, Ying-Hsiang / Chen, Yi-Song / Chen, Yuh-Min / Chien, Li-Hsin / Chirlaque, María-Dolores / Choi, Jin Eun / Choi, Yi Young / Chow, Wong-Ho / Chung, Charles C / Clavel, Jacqueline / Clavel-Chapelon, Françoise / Cocco, Pierluigi / Colt, Joanne S / Comperat, Eva / Conde, Lucia / Connors, Joseph M / Conti, David / Cortessis, Victoria K / Cotterchio, Michelle / Cozen, Wendy / Crouch, Simon / Crous-Bou, Marta / Cussenot, Olivier / Davis, Faith G / Ding, Ti / Diver, W Ryan / Dorronsoro, Miren / Dossus, Laure / Duell, Eric J / Ennas, Maria Grazia / Erickson, Ralph L / Feychting, Maria / Flanagan, Adrienne M / Foretova, Lenka / Fraumeni, Joseph F / Freedman, Neal D / Beane Freeman, Laura E / Fuchs, Charles / Gago-Dominguez, Manuela / Gallinger, Steven / Gao, Yu-Tang / Gapstur, Susan M / Garcia-Closas, Montserrat / García-Closas, Reina / Gascoyne, Randy D / Gastier-Foster, Julie / Gaudet, Mia M / Gaziano, J Michael / Giffen, Carol / Giles, Graham G / Giovannucci, Edward / Glimelius, Bengt / Goggins, Michael / Gokgoz, Nalan / Goldstein, Alisa M / Gorlick, Richard / Gross, Myron / Grubb, Robert / Gu, Jian / Guan, Peng / Gunter, Marc / Guo, Huan / Habermann, Thomas M / Haiman, Christopher A / Halai, Dina / Hallmans, Goran / Hassan, Manal / Hattinger, Claudia / He, Qincheng / He, Xingzhou / Helzlsouer, Kathy / Henderson, Brian / Henriksson, Roger / Hjalgrim, Henrik / Hoffman-Bolton, Judith / Hohensee, Chancellor / Holford, Theodore R / Holly, Elizabeth A / Hong, Yun-Chul / Hoover, Robert N / Horn-Ross, Pamela L / Hosain, G M Monawar / Hosgood, H Dean / Hsiao, Chin-Fu / Hu, Nan / Hu, Wei / Hu, Zhibin / Huang, Ming-Shyan / Huerta, Jose-Maria / Hung, Jen-Yu / Hutchinson, Amy / Inskip, Peter D / Jackson, Rebecca D / Jacobs, Eric J / Jenab, Mazda / Jeon, Hyo-Sung / Ji, Bu-Tian / Jin, Guangfu / Jin, Li / Johansen, Christoffer / Johnson, Alison / Jung, Yoo Jin / Kaaks, Rudolph / Kamineni, Aruna / Kane, Eleanor / Kang, Chang Hyun / Karagas, Margaret R / Kelly, Rachel S / Khaw, Kay-Tee / Kim, Christopher / Kim, Hee Nam / Kim, Jin Hee / Kim, Jun Suk / Kim, Yeul Hong / Kim, Young Tae / Kim, Young-Chul / Kitahara, Cari M / Klein, Alison P / Klein, Robert J / Kogevinas, Manolis / Kohno, Takashi / Kolonel, Laurence N / Kooperberg, Charles / Kricker, Anne / Krogh, Vittorio / Kunitoh, Hideo / Kurtz, Robert C / Kweon, Sun-Seog / LaCroix, Andrea / Lawrence, Charles / Lecanda, Fernando / Lee, Victor Ho Fun / Li, Donghui / Li, Haixin / Li, Jihua / Li, Yao-Jen / Li, Yuqing / Liao, Linda M / Liebow, Mark / Lightfoot, Tracy / Lim, Wei-Yen / Lin, Chien-Chung / Lin, Dongxin / Lindstrom, Sara / Linet, Martha S / Link, Brian K / Liu, Chenwei / Liu, Jianjun / Liu, Li / Ljungberg, Börje / Lloreta, Josep / Di Lollo, Simonetta / Lu, Daru / Lund, Eiluv / Malats, Nuria / Mannisto, Satu / Le Marchand, Loic / Marina, Neyssa / Masala, Giovanna / Mastrangelo, Giuseppe / Matsuo, Keitaro / Maynadie, Marc / McKay, James / McKean-Cowdin, Roberta / Melbye, Mads / Melin, Beatrice S / Michaud, Dominique S / Mitsudomi, Tetsuya / Monnereau, Alain / Montalvan, Rebecca / Moore, Lee E / Mortensen, Lotte Maxild / Nieters, Alexandra / North, Kari E / Novak, Anne J / Oberg, Ann L / Offit, Kenneth / Oh, In-Jae / Olson, Sara H / Palli, Domenico / Pao, William / Park, In Kyu / Park, Jae Yong / Park, Kyong Hwa / Patiño-Garcia, Ana / Pavanello, Sofia / Peeters, Petra H M / Perng, Reury-Perng / Peters, Ulrike / Petersen, Gloria M / Picci, Piero / Pike, Malcolm C / Porru, Stefano / Prescott, Jennifer / Prokunina-Olsson, Ludmila / Qian, Biyun / Qiao, You-Lin / Rais, Marco / Riboli, Elio / Riby, Jacques / Risch, Harvey A / Rizzato, Cosmeri / Rodabough, Rebecca / Roman, Eve / Roupret, Morgan / Ruder, Avima M / Sanjose, Silvia de / Scelo, Ghislaine / Schned, Alan / Schumacher, Fredrick / Schwartz, Kendra / Schwenn, Molly / Scotlandi, Katia / Seow, Adeline / Serra, Consol / Serra, Massimo / Sesso, Howard D / Setiawan, Veronica Wendy / Severi, Gianluca / Severson, Richard K / Shanafelt, Tait D / Shen, Hongbing / Shen, Wei / Shin, Min-Ho / Shiraishi, Kouya / Shu, Xiao-Ou / Siddiq, Afshan / Sierrasesúmaga, Luis / Sihoe, Alan Dart Loon / Skibola, Christine F / Smith, Alex / Smith, Martyn T / Southey, Melissa C / Spinelli, John J / Staines, Anthony / Stampfer, Meir / Stern, Marianna C / Stevens, Victoria L / Stolzenberg-Solomon, Rachael S / Su, Jian / Su, Wu-Chou / Sund, Malin / Sung, Jae Sook / Sung, Sook Whan / Tan, Wen / Tang, Wei / Tardón, Adonina / Thomas, David / Thompson, Carrie A / Tinker, Lesley F / Tirabosco, Roberto / Tjønneland, Anne / Travis, Ruth C / Trichopoulos, Dimitrios / Tsai, Fang-Yu / Tsai, Ying-Huang / Tucker, Margaret / Turner, Jenny / Vajdic, Claire M / Vermeulen, Roel C H / Villano, Danylo J / Vineis, Paolo / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chaoyu / Wang, Chih-Liang / Wang, Jiu-Cun / Wang, Junwen / Wei, Fusheng / Weiderpass, Elisabete / Weiner, George J / Weinstein, Stephanie / Wentzensen, Nicolas / White, Emily / Witzig, Thomas E / Wolpin, Brian M / Wong, Maria Pik / Wu, Chen / Wu, Guoping / Wu, Junjie / Wu, Tangchun / Wu, Wei / Wu, Xifeng / Wu, Yi-Long / Wunder, Jay S / Xiang, Yong-Bing / Xu, Jun / Xu, Ping / Yang, Pan-Chyr / Yang, Tsung-Ying / Ye, Yuanqing / Yin, Zhihua / Yokota, Jun / Yoon, Ho-Il / Yu, Chong-Jen / Yu, Herbert / Yu, Kai / Yuan, Jian-Min / Zelenetz, Andrew / Zeleniuch-Jacquotte, Anne / Zhang, Xu-Chao / Zhang, Yawei / Zhao, Xueying / Zhao, Zhenhong / Zheng, Hong / Zheng, Tongzhang / Zheng, Wei / Zhou, Baosen / Zhu, Meng / Zucca, Mariagrazia / Boca, Simina M / Cerhan, James R / Ferri, Giovanni M / Hartge, Patricia / Hsiung, Chao Agnes / Magnani, Corrado / Miligi, Lucia / Morton, Lindsay M / Smedby, Karin E / Teras, Lauren R / Vijai, Joseph / Wang, Sophia S / Brennan, Paul / Caporaso, Neil E / Hunter, David J / Kraft, Peter / Rothman, Nathaniel / Silverman, Debra T / Slager, Susan L / Chanock, Stephen J / Chatterjee, Nilanjan

    Journal of the National Cancer Institute

    2015  Volume 107, Issue 12, Page(s) djv279

    Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms ( ...

    Abstract Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
    Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
    Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.
    Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
    MeSH term(s) Adult ; Aged ; Asian People/genetics ; Asian People/statistics & numerical data ; Bone Neoplasms/genetics ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Kidney Neoplasms/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Lung Neoplasms/etiology ; Lung Neoplasms/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Male ; Middle Aged ; Neoplasms/etiology ; Neoplasms/genetics ; Osteosarcoma/genetics ; Polymorphism, Single Nucleotide ; Smoking/adverse effects ; Testicular Neoplasms/genetics ; Tissue Array Analysis ; Urinary Bladder Neoplasms/etiology ; Urinary Bladder Neoplasms/genetics ; White People/genetics ; White People/statistics & numerical data
    Language English
    Publishing date 2015-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2992-0
    ISSN 1460-2105 ; 0027-8874 ; 0198-0157
    ISSN (online) 1460-2105
    ISSN 0027-8874 ; 0198-0157
    DOI 10.1093/jnci/djv279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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