Abstract
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 431 |
| Tidsskrift | Nature Communications |
| Vol/bind | 10 |
| Udgave nummer | 1 |
| Antal sider | 23 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 25 jan. 2019 |
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- 10.1038/s41467-018-08054-4Licens: CC BY
- Shared heritability and functional enrichment across six solid cancersForlagets udgivne version, 3,74 MBLicens: CC BY
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Shared heritability and functional enrichment across six solid cancers. / Jiang, Xia; Finucane, Hilary K; Schumacher, Fredrick R; Schmit, Stephanie L; Tyrer, Jonathan P; Han, Younghun; Michailidou, Kyriaki; Lesseur, Corina; Kuchenbaecker, Karoline B; Dennis, Joe; Conti, David V; Casey, Graham; Gaudet, Mia M; Huyghe, Jeroen R; Albanes, Demetrius; Aldrich, Melinda C; Andrew, Angeline S; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Antonenkova, Natalia N; Arnold, Susanne M; Aronson, Kristan J; Arun, Banu K; Bandera, Elisa V; Barkardottir, Rosa B; Barnes, Daniel R; Batra, Jyotsna; Beckmann, Matthias W; Benitez, Javier; Benlloch, Sara; Berchuck, Andrew; Berndt, Sonja I; Bickeböller, Heike; Bien, Stephanie A; Blomqvist, Carl; Boccia, Stefania; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Brauch, Hiltrud; Brenner, Hermann; Brenton, James D; Brook, Mark N; Brunet, Joan; Brunnström, Hans; Buchanan, Daniel D; Burwinkel, Barbara; Butzow, Ralf; Cadoni, Gabriella; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Campbell, Peter T; Cancel-Tassin, Géraldine; Cannon-Albright, Lisa; Campa, Daniele; Caporaso, Neil; Carvalho, André L; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Chu; Christiani, David C; Claes, Kathleen B M; Claessens, Frank; Clements, Judith; Collée, J Margriet; Correa, Marcia Cruz; Couch, Fergus J; Cox, Angela; Cunningham, Julie M; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; deFazio, Anna; Devilee, Peter; Diez, Orland; Gago-Dominguez, Manuela; Donovan, Jenny L; Dörk, Thilo; Duell, Eric J; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Edlund, Christopher K; Edwards, Digna R Velez; Ellberg, Carolina; Evans, D Gareth; Fasching, Peter A; Ferris, Robert L; Liloglou, Triantafillos; Figueiredo, Jane C; Fletcher, Olivia; Fortner, Renée T; Fostira, Florentia; Franceschi, Silvia; Friedman, Eitan; Gallinger, Steven J; Ganz, Patricia A; Garber, Judy; García-Sáenz, José A; Gayther, Simon A; Giles, Graham G; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; Goode, Ellen L; Goodman, Marc T; Goodman, Gary; Grankvist, Kjell; Greene, Mark H; Gronberg, Henrik; Gronwald, Jacek; Guénel, Pascal; Håkansson, Niclas; Hall, Per; Hamann, Ute; Hamdy, Freddie C; Hamilton, Robert J; Hampe, Jochen; Haugen, Aage; Heitz, Florian; Herrero, Rolando; Hillemanns, Peter; Hoffmeister, Michael; Høgdall, Estrid; Hong, Yun-Chul; Hopper, John L; Houlston, Richard; Hulick, Peter J; Hunter, David J; Huntsman, David G; Idos, Gregory; Imyanitov, Evgeny N; Ingles, Sue Ann; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Jenkins, Mark A; Johansson, Mattias; Johansson, Mikael; John, Esther M; Joshi, Amit D; Kaneva, Radka; Karlan, Beth Y; Kelemen, Linda E; Kühl, Tabea; Khaw, Kay-Tee; Khusnutdinova, Elza; Kibel, Adam S; Kiemeney, Lambertus A; Kim, Jeri; Kjaer, Susanne K; Knight, Julia A; Kogevinas, Manolis; Kote-Jarai, Zsofia; Koutros, Stella; Kristensen, Vessela N; Kupryjanczyk, Jolanta; Lacko, Martin; Lam, Stephan; Lambrechts, Diether; Landi, Maria Teresa; Lazarus, Philip; Le, Nhu D; Lee, Eunjung; Lejbkowicz, Flavio; Lenz, Heinz-Josef; Leslie, Goska; Lessel, Davor; Lester, Jenny; Levine, Douglas A; Li, Li; Li, Christopher I; Lindblom, Annika; Lindor, Noralane M; Liu, Geoffrey; Loupakis, Fotios; Lubiński, Jan; Maehle, Lovise; Maier, Christiane; Mannermaa, Arto; Marchand, Loic Le; Margolin, Sara; May, Taymaa; McGuffog, Lesley; Meindl, Alfons; Middha, Pooja; Miller, Austin; Milne, Roger L; MacInnis, Robert J; Modugno, Francesmary; Montagna, Marco; Moreno, Victor; Moysich, Kirsten B; Mucci, Lorelei; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Neal, David E; Ness, Andrew R; Neuhausen, Susan L; Nevanlinna, Heli; Newcomb, Polly A; Newcomb, Lisa F; Nielsen, Finn Cilius; Nikitina-Zake, Liene; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olama, Ali Amin Al; Olopade, Olufunmilayo I; Olshan, Andrew F; Olsson, Håkan; Osorio, Ana; Pandha, Hardev; Park, Jong Y; Pashayan, Nora; Parsons, Michael T; Pejovic, Tanja; Penney, Kathryn L; Peters, Wilbert H M; Phelan, Catherine M; Phipps, Amanda I; Plaseska-Karanfilska, Dijana; Pring, Miranda; Prokofyeva, Darya; Radice, Paolo; Stefansson, Kari; Ramus, Susan J; Raskin, Leon; Rennert, Gad; Rennert, Hedy S; van Rensburg, Elizabeth J; Riggan, Marjorie J; Risch, Harvey A; Risch, Angela; Roobol, Monique J; Rosenstein, Barry S; Rossing, Mary Anne; De Ruyck, Kim; Saloustros, Emmanouil; Sandler, Dale P; Sawyer, Elinor J; Schabath, Matthew B; Schleutker, Johanna; Schmidt, Marjanka K; Setiawan, V Wendy; Shen, Hongbing; Siegel, Erin M; Sieh, Weiva; Singer, Christian F; Slattery, Martha L; Sorensen, Karina Dalsgaard; Southey, Melissa C; Spurdle, Amanda B; Stanford, Janet L; Stevens, Victoria L; Stintzing, Sebastian; Stone, Jennifer; Sundfeldt, Karin; Sutphen, Rebecca; Swerdlow, Anthony J; Tajara, Eloiza H; Tangen, Catherine M; Tardon, Adonina; Taylor, Jack A; Teare, M Dawn; Teixeira, Manuel R; Terry, Mary Beth; Terry, Kathryn L; Thibodeau, Stephen N; Thomassen, Mads; Bjørge, Line; Tischkowitz, Marc; Toland, Amanda E; Torres, Diana; Townsend, Paul A; Travis, Ruth C; Tung, Nadine; Tworoger, Shelley S; Ulrich, Cornelia M; Usmani, Nawaid; Vachon, Celine M; Van Nieuwenhuysen, Els; Vega, Ana; Aguado-Barrera, Miguel Elías; Wang, Qin; Webb, Penelope M; Weinberg, Clarice R; Weinstein, Stephanie; Weissler, Mark C; Weitzel, Jeffrey N; West, Catharine M L; White, Emily; Whittemore, Alice S; Wichmann, H-Erich; Wiklund, Fredrik; Winqvist, Robert; Wolk, Alicja; Woll, Penella; Woods, Michael; Wu, Anna H; Wu, Xifeng; Yannoukakos, Drakoulis; Zheng, Wei; Zienolddiny, Shanbeh; Ziogas, Argyrios; Zorn, Kristin K; Lane, Jacqueline M; Saxena, Richa; Thomas, Duncan; Hung, Rayjean J; Diergaarde, Brenda; McKay, James; Peters, Ulrike; Hsu, Li; García-Closas, Montserrat; Eeles, Rosalind A; Chenevix-Trench, Georgia; Brennan, Paul J; Haiman, Christopher A; Simard, Jacques; Easton, Douglas F; Gruber, Stephen B; Pharoah, Paul D P; Price, Alkes L; Pasaniuc, Bogdan; Amos, Christopher I; Kraft, Peter; Lindström, Sara.
I: Nature Communications, Bind 10, Nr. 1, 431, 25.01.2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Shared heritability and functional enrichment across six solid cancers
AU - Jiang, Xia
AU - Finucane, Hilary K
AU - Schumacher, Fredrick R
AU - Schmit, Stephanie L
AU - Tyrer, Jonathan P
AU - Han, Younghun
AU - Michailidou, Kyriaki
AU - Lesseur, Corina
AU - Kuchenbaecker, Karoline B
AU - Dennis, Joe
AU - Conti, David V
AU - Casey, Graham
AU - Gaudet, Mia M
AU - Huyghe, Jeroen R
AU - Albanes, Demetrius
AU - Aldrich, Melinda C
AU - Andrew, Angeline S
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C
AU - Antonenkova, Natalia N
AU - Arnold, Susanne M
AU - Aronson, Kristan J
AU - Arun, Banu K
AU - Bandera, Elisa V
AU - Barkardottir, Rosa B
AU - Barnes, Daniel R
AU - Batra, Jyotsna
AU - Beckmann, Matthias W
AU - Benitez, Javier
AU - Benlloch, Sara
AU - Berchuck, Andrew
AU - Berndt, Sonja I
AU - Bickeböller, Heike
AU - Bien, Stephanie A
AU - Blomqvist, Carl
AU - Boccia, Stefania
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Bolla, Manjeet K
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brenton, James D
AU - Brook, Mark N
AU - Brunet, Joan
AU - Brunnström, Hans
AU - Buchanan, Daniel D
AU - Burwinkel, Barbara
AU - Butzow, Ralf
AU - Cadoni, Gabriella
AU - Caldés, Trinidad
AU - Caligo, Maria A
AU - Campbell, Ian
AU - Campbell, Peter T
AU - Cancel-Tassin, Géraldine
AU - Cannon-Albright, Lisa
AU - Campa, Daniele
AU - Caporaso, Neil
AU - Carvalho, André L
AU - Chan, Andrew T
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J
AU - Chen, Chu
AU - Christiani, David C
AU - Claes, Kathleen B M
AU - Claessens, Frank
AU - Clements, Judith
AU - Collée, J Margriet
AU - Correa, Marcia Cruz
AU - Couch, Fergus J
AU - Cox, Angela
AU - Cunningham, Julie M
AU - Cybulski, Cezary
AU - Czene, Kamila
AU - Daly, Mary B
AU - deFazio, Anna
AU - Devilee, Peter
AU - Diez, Orland
AU - Gago-Dominguez, Manuela
AU - Donovan, Jenny L
AU - Dörk, Thilo
AU - Duell, Eric J
AU - Dunning, Alison M
AU - Dwek, Miriam
AU - Eccles, Diana M
AU - Edlund, Christopher K
AU - Edwards, Digna R Velez
AU - Ellberg, Carolina
AU - Evans, D Gareth
AU - Fasching, Peter A
AU - Ferris, Robert L
AU - Liloglou, Triantafillos
AU - Figueiredo, Jane C
AU - Fletcher, Olivia
AU - Fortner, Renée T
AU - Fostira, Florentia
AU - Franceschi, Silvia
AU - Friedman, Eitan
AU - Gallinger, Steven J
AU - Ganz, Patricia A
AU - Garber, Judy
AU - García-Sáenz, José A
AU - Gayther, Simon A
AU - Giles, Graham G
AU - Godwin, Andrew K
AU - Goldberg, Mark S
AU - Goldgar, David E
AU - Goode, Ellen L
AU - Goodman, Marc T
AU - Goodman, Gary
AU - Grankvist, Kjell
AU - Greene, Mark H
AU - Gronberg, Henrik
AU - Gronwald, Jacek
AU - Guénel, Pascal
AU - Håkansson, Niclas
AU - Hall, Per
AU - Hamann, Ute
AU - Hamdy, Freddie C
AU - Hamilton, Robert J
AU - Hampe, Jochen
AU - Haugen, Aage
AU - Heitz, Florian
AU - Herrero, Rolando
AU - Hillemanns, Peter
AU - Hoffmeister, Michael
AU - Høgdall, Estrid
AU - Hong, Yun-Chul
AU - Hopper, John L
AU - Houlston, Richard
AU - Hulick, Peter J
AU - Hunter, David J
AU - Huntsman, David G
AU - Idos, Gregory
AU - Imyanitov, Evgeny N
AU - Ingles, Sue Ann
AU - Isaacs, Claudine
AU - Jakubowska, Anna
AU - James, Paul
AU - Jenkins, Mark A
AU - Johansson, Mattias
AU - Johansson, Mikael
AU - John, Esther M
AU - Joshi, Amit D
AU - Kaneva, Radka
AU - Karlan, Beth Y
AU - Kelemen, Linda E
AU - Kühl, Tabea
AU - Khaw, Kay-Tee
AU - Khusnutdinova, Elza
AU - Kibel, Adam S
AU - Kiemeney, Lambertus A
AU - Kim, Jeri
AU - Kjaer, Susanne K
AU - Knight, Julia A
AU - Kogevinas, Manolis
AU - Kote-Jarai, Zsofia
AU - Koutros, Stella
AU - Kristensen, Vessela N
AU - Kupryjanczyk, Jolanta
AU - Lacko, Martin
AU - Lam, Stephan
AU - Lambrechts, Diether
AU - Landi, Maria Teresa
AU - Lazarus, Philip
AU - Le, Nhu D
AU - Lee, Eunjung
AU - Lejbkowicz, Flavio
AU - Lenz, Heinz-Josef
AU - Leslie, Goska
AU - Lessel, Davor
AU - Lester, Jenny
AU - Levine, Douglas A
AU - Li, Li
AU - Li, Christopher I
AU - Lindblom, Annika
AU - Lindor, Noralane M
AU - Liu, Geoffrey
AU - Loupakis, Fotios
AU - Lubiński, Jan
AU - Maehle, Lovise
AU - Maier, Christiane
AU - Mannermaa, Arto
AU - Marchand, Loic Le
AU - Margolin, Sara
AU - May, Taymaa
AU - McGuffog, Lesley
AU - Meindl, Alfons
AU - Middha, Pooja
AU - Miller, Austin
AU - Milne, Roger L
AU - MacInnis, Robert J
AU - Modugno, Francesmary
AU - Montagna, Marco
AU - Moreno, Victor
AU - Moysich, Kirsten B
AU - Mucci, Lorelei
AU - Muir, Kenneth
AU - Mulligan, Anna Marie
AU - Nathanson, Katherine L
AU - Neal, David E
AU - Ness, Andrew R
AU - Neuhausen, Susan L
AU - Nevanlinna, Heli
AU - Newcomb, Polly A
AU - Newcomb, Lisa F
AU - Nielsen, Finn Cilius
AU - Nikitina-Zake, Liene
AU - Nordestgaard, Børge G
AU - Nussbaum, Robert L
AU - Offit, Kenneth
AU - Olah, Edith
AU - Olama, Ali Amin Al
AU - Olopade, Olufunmilayo I
AU - Olshan, Andrew F
AU - Olsson, Håkan
AU - Osorio, Ana
AU - Pandha, Hardev
AU - Park, Jong Y
AU - Pashayan, Nora
AU - Parsons, Michael T
AU - Pejovic, Tanja
AU - Penney, Kathryn L
AU - Peters, Wilbert H M
AU - Phelan, Catherine M
AU - Phipps, Amanda I
AU - Plaseska-Karanfilska, Dijana
AU - Pring, Miranda
AU - Prokofyeva, Darya
AU - Radice, Paolo
AU - Stefansson, Kari
AU - Ramus, Susan J
AU - Raskin, Leon
AU - Rennert, Gad
AU - Rennert, Hedy S
AU - van Rensburg, Elizabeth J
AU - Riggan, Marjorie J
AU - Risch, Harvey A
AU - Risch, Angela
AU - Roobol, Monique J
AU - Rosenstein, Barry S
AU - Rossing, Mary Anne
AU - De Ruyck, Kim
AU - Saloustros, Emmanouil
AU - Sandler, Dale P
AU - Sawyer, Elinor J
AU - Schabath, Matthew B
AU - Schleutker, Johanna
AU - Schmidt, Marjanka K
AU - Setiawan, V Wendy
AU - Shen, Hongbing
AU - Siegel, Erin M
AU - Sieh, Weiva
AU - Singer, Christian F
AU - Slattery, Martha L
AU - Sorensen, Karina Dalsgaard
AU - Southey, Melissa C
AU - Spurdle, Amanda B
AU - Stanford, Janet L
AU - Stevens, Victoria L
AU - Stintzing, Sebastian
AU - Stone, Jennifer
AU - Sundfeldt, Karin
AU - Sutphen, Rebecca
AU - Swerdlow, Anthony J
AU - Tajara, Eloiza H
AU - Tangen, Catherine M
AU - Tardon, Adonina
AU - Taylor, Jack A
AU - Teare, M Dawn
AU - Teixeira, Manuel R
AU - Terry, Mary Beth
AU - Terry, Kathryn L
AU - Thibodeau, Stephen N
AU - Thomassen, Mads
AU - Bjørge, Line
AU - Tischkowitz, Marc
AU - Toland, Amanda E
AU - Torres, Diana
AU - Townsend, Paul A
AU - Travis, Ruth C
AU - Tung, Nadine
AU - Tworoger, Shelley S
AU - Ulrich, Cornelia M
AU - Usmani, Nawaid
AU - Vachon, Celine M
AU - Van Nieuwenhuysen, Els
AU - Vega, Ana
AU - Aguado-Barrera, Miguel Elías
AU - Wang, Qin
AU - Webb, Penelope M
AU - Weinberg, Clarice R
AU - Weinstein, Stephanie
AU - Weissler, Mark C
AU - Weitzel, Jeffrey N
AU - West, Catharine M L
AU - White, Emily
AU - Whittemore, Alice S
AU - Wichmann, H-Erich
AU - Wiklund, Fredrik
AU - Winqvist, Robert
AU - Wolk, Alicja
AU - Woll, Penella
AU - Woods, Michael
AU - Wu, Anna H
AU - Wu, Xifeng
AU - Yannoukakos, Drakoulis
AU - Zheng, Wei
AU - Zienolddiny, Shanbeh
AU - Ziogas, Argyrios
AU - Zorn, Kristin K
AU - Lane, Jacqueline M
AU - Saxena, Richa
AU - Thomas, Duncan
AU - Hung, Rayjean J
AU - Diergaarde, Brenda
AU - McKay, James
AU - Peters, Ulrike
AU - Hsu, Li
AU - García-Closas, Montserrat
AU - Eeles, Rosalind A
AU - Chenevix-Trench, Georgia
AU - Brennan, Paul J
AU - Haiman, Christopher A
AU - Simard, Jacques
AU - Easton, Douglas F
AU - Gruber, Stephen B
AU - Pharoah, Paul D P
AU - Price, Alkes L
AU - Pasaniuc, Bogdan
AU - Amos, Christopher I
AU - Kraft, Peter
AU - Lindström, Sara
PY - 2019/1/25
Y1 - 2019/1/25
N2 - Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
AB - Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
KW - Breast Neoplasms/diagnosis
KW - Case-Control Studies
KW - Colorectal Neoplasms/diagnosis
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Head and Neck Neoplasms/diagnosis
KW - Humans
KW - Inheritance Patterns
KW - Lung Neoplasms/diagnosis
KW - Male
KW - Mental Disorders/ethnology
KW - Neoplasm Proteins/genetics
KW - Ovarian Neoplasms/diagnosis
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Prostatic Neoplasms/diagnosis
KW - Smoking/ethnology
UR - https://www.nature.com/articles/s41467-019-12095-8
U2 - 10.1038/s41467-018-08054-4
DO - 10.1038/s41467-018-08054-4
M3 - Journal article
C2 - 30683880
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 431
ER -