MicroRNA related polymorphisms and breast cancer risk

Sofia Khan; Dario Greco; Kyriaki Michailidou; Roger L. Milne; Taru A. Muranen; Tuomas Heikkinen; Kirsimari Aaltonen; Joe Dennis; Manjeet K. Bolla; Jianjun Liu; Per Hall; Astrid Irwanto; Keith Humphreys; Jingmei Li; Kamila Czene; Jenny Chang-Claude; Rebecca Hein; Anja Rudolph; Petra Seibold; Dieter Flesch-Janys; Olivia Fletcher; Julian Peto; Isabel Dos Santos Silva; Nichola Johnson; Lorna Gibson; Zoe Aitken; John L. Hopper; Helen Tsimiklis; Minh Bui; Enes Makalic; Daniel F. Schmidt; Melissa C. Southey; Carmel Apicella; Jennifer Stone; Quinten Waisfisz; Hanne Meijers-Heijboer; Muriel A. Adank; Rob B. Van Der Luijt; Alfons Meindl; Rita K. Schmutzler; Bertram Müller-Myhsok; Peter Lichtner; Clare Turnbull; Nazneen Rahman; Stephen J. Chanock; David J. Hunter; Angela Cox; Simon S. Cross; Malcolm W.R. Reed; Marjanka K. Schmidt; Annegien Broeks; Laura J. Van'T Veer; Frans B. Hogervorst; Peter A. Fasching; Michael G. Schrauder; Arif B. Ekici; Matthias W. Beckmann; Stig E. Bojesen; Børge G. Nordestgaard; Sune F. Nielsen; Henrik Flyger; Javier Benitez; Pilar M. Zamora; Jose I.A. Perez; Christopher A. Haiman; Brian E. Henderson; Fredrick Schumacher; Loic Le March; Paul D.P. Pharoah; Alison M. Dunning; Mitul Shah; Robert Luben; Judith Brown; Fergus J. Couch; Xianshu Wang; Celine Vachon; Janet E. Olson; Diether Lambrechts; Matthieu Moisse; Robert Paridaens; Marie Rose Christiaens; Pascal Guénel; Thérèse Truong; Pierre Laurent-Puig; Claire Mulot; Frederick Marme; Barbara Burwinkel; Andreas Schneeweiss; Christof Sohn; Elinor J. Sawyer; Ian Tomlinson; Michael J. Kerin; Nicola Miller; Irene L. Andrulis; Julia A. Knight; Srine Tchatchou; Anna Marie Mulligan; Thilo Dörk; Natalia V. Bogdanova; Natalia N. Antonenkova; Hoda Anton-Culver; Hatef Darabi; Mikael Eriksson; Montserrat Garcia-Closas; Jonine Figueroa; Jolanta Lissowska; Louise Brinton; Peter Devilee; Robert A.E.M. Tollenaar; Caroline Seynaeve; Christi J. Van Asperen; Vessela N. Kristensen; Susan Slager Australian Ovarian Cancer Study Group; Ama E. Tol; Christine B. Ambrosone; Drakoulis Yannoukakos; Annika Lindblom; Sara Margolin; Paolo Radice; Paolo Peterlongo; Monica Barile; Paolo Mariani; Maartje J. Hooning; John W.M. Martens; J. Margriet Collée; Agnes Jager; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska-Bieniek; Katarzyna Durda; Graham G. Giles; Catriona McLean; Hiltrud Brauch; Thomas Brüning; Yon Dschun Ko; Hermann Brenner The Genica Network; Aida Karina Dieffenbach; Volker Arndt; Christa Stegmaier; Anthony Swerdlow; Alan Ashworth; Nick Orr; Michael Jones; Jacques Simard; Mark S. Goldberg; France Labrèche; Martine Dumont; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Vesa Kataja; Veli Matti Kosma; Jaana M. Hartikainen; Arto Mannermaa; Ute Hamann; Georgia Chenevix-Trench; Carl Blomqvist; Kristiina Aittomäki; Douglas F. Easton; Heli Nevanlinna

doi:10.1371/journal.pone.0109973

MicroRNA related polymorphisms and breast cancer risk

Sofia Khan, Dario Greco, Kyriaki Michailidou, Roger L. Milne, Taru A. Muranen, Tuomas Heikkinen, Kirsimari Aaltonen, Joe Dennis, Manjeet K. Bolla, Jianjun Liu, Per Hall, Astrid Irwanto, Keith Humphreys, Jingmei Li, Kamila Czene, Jenny Chang-Claude, Rebecca Hein, Anja Rudolph, Petra Seibold, Dieter Flesch-JanysOlivia Fletcher, Julian Peto, Isabel Dos Santos Silva, Nichola Johnson, Lorna Gibson, Zoe Aitken, John L. Hopper, Helen Tsimiklis, Minh Bui, Enes Makalic, Daniel F. Schmidt, Melissa C. Southey, Carmel Apicella, Jennifer Stone, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel A. Adank, Rob B. Van Der Luijt, Alfons Meindl, Rita K. Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Clare Turnbull, Nazneen Rahman, Stephen J. Chanock, David J. Hunter, Angela Cox, Simon S. Cross, Malcolm W.R. Reed, Marjanka K. Schmidt, Annegien Broeks, Laura J. Van'T Veer, Frans B. Hogervorst, Peter A. Fasching, Michael G. Schrauder, Arif B. Ekici, Matthias W. Beckmann, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Javier Benitez, Pilar M. Zamora, Jose I.A. Perez, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le March, Paul D.P. Pharoah, Alison M. Dunning, Mitul Shah, Robert Luben, Judith Brown, Fergus J. Couch, Xianshu Wang, Celine Vachon, Janet E. Olson, Diether Lambrechts, Matthieu Moisse, Robert Paridaens, Marie Rose Christiaens, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Claire Mulot, Frederick Marme, Barbara Burwinkel, Andreas Schneeweiss, Christof Sohn, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Irene L. Andrulis, Julia A. Knight, Srine Tchatchou, Anna Marie Mulligan, Thilo Dörk, Natalia V. Bogdanova, Natalia N. Antonenkova, Hoda Anton-Culver, Hatef Darabi, Mikael Eriksson, Montserrat Garcia-Closas, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Peter Devilee, Robert A.E.M. Tollenaar, Caroline Seynaeve, Christi J. Van Asperen, Vessela N. Kristensen, Susan Slager Australian Ovarian Cancer Study Group, Ama E. Tol, Christine B. Ambrosone, Drakoulis Yannoukakos, Annika Lindblom, Sara Margolin, Paolo Radice, Paolo Peterlongo, Monica Barile, Paolo Mariani, Maartje J. Hooning, John W.M. Martens, J. Margriet Collée, Agnes Jager, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Graham G. Giles, Catriona McLean, Hiltrud Brauch, Thomas Brüning, Yon Dschun Ko, Hermann Brenner The Genica Network, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Michael Jones, Jacques Simard, Mark S. Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Arto Mannermaa, Ute Hamann, Georgia Chenevix-Trench, Carl Blomqvist, Kristiina Aittomäki, Douglas F. Easton, Heli Nevanlinna

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% Cl: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01 -1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. This is an open-access article free of all copyright.

Original language	English (US)
Article number	e109973
Journal	PloS one
Volume	9
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0109973
State	Published - Nov 12 2014

ASJC Scopus subject areas

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10.1371/journal.pone.0109973

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Khan, S., Greco, D., Michailidou, K., Milne, R. L., Muranen, T. A., Heikkinen, T., Aaltonen, K., Dennis, J., Bolla, M. K., Liu, J., Hall, P., Irwanto, A., Humphreys, K., Li, J., Czene, K., Chang-Claude, J., Hein, R., Rudolph, A., Seibold, P., ... Nevanlinna, H. (2014). MicroRNA related polymorphisms and breast cancer risk. PloS one, 9(11), Article e109973. https://doi.org/10.1371/journal.pone.0109973

Khan, S, Greco, D, Michailidou, K, Milne, RL, Muranen, TA, Heikkinen, T, Aaltonen, K, Dennis, J, Bolla, MK, Liu, J, Hall, P, Irwanto, A, Humphreys, K, Li, J, Czene, K, Chang-Claude, J, Hein, R, Rudolph, A, Seibold, P, Flesch-Janys, D, Fletcher, O, Peto, J, Silva, IDS, Johnson, N, Gibson, L, Aitken, Z, Hopper, JL, Tsimiklis, H, Bui, M, Makalic, E, Schmidt, DF, Southey, MC, Apicella, C, Stone, J, Waisfisz, Q, Meijers-Heijboer, H, Adank, MA, Van Der Luijt, RB, Meindl, A, Schmutzler, RK, Müller-Myhsok, B, Lichtner, P, Turnbull, C, Rahman, N, Chanock, SJ, Hunter, DJ, Cox, A, Cross, SS, Reed, MWR, Schmidt, MK, Broeks, A, Van'T Veer, LJ, Hogervorst, FB, Fasching, PA, Schrauder, MG, Ekici, AB, Beckmann, MW, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Benitez, J, Zamora, PM, Perez, JIA, Haiman, CA, Henderson, BE, Schumacher, F, March, LL, Pharoah, PDP, Dunning, AM, Shah, M, Luben, R, Brown, J, Couch, FJ, Wang, X, Vachon, C, Olson, JE, Lambrechts, D, Moisse, M, Paridaens, R, Christiaens, MR, Guénel, P, Truong, T, Laurent-Puig, P, Mulot, C, Marme, F, Burwinkel, B, Schneeweiss, A, Sohn, C, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Andrulis, IL, Knight, JA, Tchatchou, S, Mulligan, AM, Dörk, T, Bogdanova, NV, Antonenkova, NN, Anton-Culver, H, Darabi, H, Eriksson, M, Garcia-Closas, M, Figueroa, J, Lissowska, J, Brinton, L, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Van Asperen, CJ, Kristensen, VN, Australian Ovarian Cancer Study Group, SS, Tol, AE, Ambrosone, CB, Yannoukakos, D, Lindblom, A, Margolin, S, Radice, P, Peterlongo, P, Barile, M, Mariani, P, Hooning, MJ, Martens, JWM, Margriet Collée, J, Jager, A, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Giles, GG, McLean, C, Brauch, H, Brüning, T, Ko, YD, The Genica Network, HB, Dieffenbach, AK, Arndt, V, Stegmaier, C, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Kataja, V, Kosma, VM, Hartikainen, JM, Mannermaa, A, Hamann, U, Chenevix-Trench, G, Blomqvist, C, Aittomäki, K, Easton, DF & Nevanlinna, H 2014, 'MicroRNA related polymorphisms and breast cancer risk', PloS one, vol. 9, no. 11, e109973. https://doi.org/10.1371/journal.pone.0109973

@article{50d765a14e34413bb8346c070f2b60af,

title = "MicroRNA related polymorphisms and breast cancer risk",

abstract = "Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% Cl: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01 -1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. This is an open-access article free of all copyright.",

author = "Sofia Khan and Dario Greco and Kyriaki Michailidou and Milne, {Roger L.} and Muranen, {Taru A.} and Tuomas Heikkinen and Kirsimari Aaltonen and Joe Dennis and Bolla, {Manjeet K.} and Jianjun Liu and Per Hall and Astrid Irwanto and Keith Humphreys and Jingmei Li and Kamila Czene and Jenny Chang-Claude and Rebecca Hein and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Olivia Fletcher and Julian Peto and Silva, {Isabel Dos Santos} and Nichola Johnson and Lorna Gibson and Zoe Aitken and Hopper, {John L.} and Helen Tsimiklis and Minh Bui and Enes Makalic and Schmidt, {Daniel F.} and Southey, {Melissa C.} and Carmel Apicella and Jennifer Stone and Quinten Waisfisz and Hanne Meijers-Heijboer and Adank, {Muriel A.} and {Van Der Luijt}, {Rob B.} and Alfons Meindl and Schmutzler, {Rita K.} and Bertram M{\"u}ller-Myhsok and Peter Lichtner and Clare Turnbull and Nazneen Rahman and Chanock, {Stephen J.} and Hunter, {David J.} and Angela Cox and Cross, {Simon S.} and Reed, {Malcolm W.R.} and Schmidt, {Marjanka K.} and Annegien Broeks and {Van'T Veer}, {Laura J.} and Hogervorst, {Frans B.} and Fasching, {Peter A.} and Schrauder, {Michael G.} and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Henrik Flyger and Javier Benitez and Zamora, {Pilar M.} and Perez, {Jose I.A.} and Haiman, {Christopher A.} and Henderson, {Brian E.} and Fredrick Schumacher and March, {Loic Le} and Pharoah, {Paul D.P.} and Dunning, {Alison M.} and Mitul Shah and Robert Luben and Judith Brown and Couch, {Fergus J.} and Xianshu Wang and Celine Vachon and Olson, {Janet E.} and Diether Lambrechts and Matthieu Moisse and Robert Paridaens and Christiaens, {Marie Rose} and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Pierre Laurent-Puig and Claire Mulot and Frederick Marme and Barbara Burwinkel and Andreas Schneeweiss and Christof Sohn and Sawyer, {Elinor J.} and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and Andrulis, {Irene L.} and Knight, {Julia A.} and Srine Tchatchou and Mulligan, {Anna Marie} and Thilo D{\"o}rk and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Hoda Anton-Culver and Hatef Darabi and Mikael Eriksson and Montserrat Garcia-Closas and Jonine Figueroa and Jolanta Lissowska and Louise Brinton and Peter Devilee and Tollenaar, {Robert A.E.M.} and Caroline Seynaeve and {Van Asperen}, {Christi J.} and Kristensen, {Vessela N.} and {Australian Ovarian Cancer Study Group}, {Susan Slager} and Tol, {Ama E.} and Ambrosone, {Christine B.} and Drakoulis Yannoukakos and Annika Lindblom and Sara Margolin and Paolo Radice and Paolo Peterlongo and Monica Barile and Paolo Mariani and Hooning, {Maartje J.} and Martens, {John W.M.} and {Margriet Coll{\'e}e}, J. and Agnes Jager and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Giles, {Graham G.} and Catriona McLean and Hiltrud Brauch and Thomas Br{\"u}ning and Ko, {Yon Dschun} and {The Genica Network}, {Hermann Brenner} and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Anthony Swerdlow and Alan Ashworth and Nick Orr and Michael Jones and Jacques Simard and Goldberg, {Mark S.} and France Labr{\`e}che and Martine Dumont and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Arto Mannermaa and Ute Hamann and Georgia Chenevix-Trench and Carl Blomqvist and Kristiina Aittom{\"a}ki and Easton, {Douglas F.} and Heli Nevanlinna",

year = "2014",

month = nov,

day = "12",

doi = "10.1371/journal.pone.0109973",

language = "English (US)",

volume = "9",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "11",

}

TY - JOUR

T1 - MicroRNA related polymorphisms and breast cancer risk

AU - Khan, Sofia

AU - Greco, Dario

AU - Michailidou, Kyriaki

AU - Milne, Roger L.

AU - Muranen, Taru A.

AU - Heikkinen, Tuomas

AU - Aaltonen, Kirsimari

AU - Dennis, Joe

AU - Bolla, Manjeet K.

AU - Liu, Jianjun

AU - Hall, Per

AU - Irwanto, Astrid

AU - Humphreys, Keith

AU - Li, Jingmei

AU - Czene, Kamila

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Peto, Julian

AU - Silva, Isabel Dos Santos

AU - Johnson, Nichola

AU - Gibson, Lorna

AU - Aitken, Zoe

AU - Hopper, John L.

AU - Tsimiklis, Helen

AU - Bui, Minh

AU - Makalic, Enes

AU - Schmidt, Daniel F.

AU - Southey, Melissa C.

AU - Apicella, Carmel

AU - Stone, Jennifer

AU - Waisfisz, Quinten

AU - Meijers-Heijboer, Hanne

AU - Adank, Muriel A.

AU - Van Der Luijt, Rob B.

AU - Meindl, Alfons

AU - Schmutzler, Rita K.

AU - Müller-Myhsok, Bertram

AU - Lichtner, Peter

AU - Turnbull, Clare

AU - Rahman, Nazneen

AU - Chanock, Stephen J.

AU - Hunter, David J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Reed, Malcolm W.R.

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Van'T Veer, Laura J.

AU - Hogervorst, Frans B.

AU - Fasching, Peter A.

AU - Schrauder, Michael G.

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Flyger, Henrik

AU - Benitez, Javier

AU - Zamora, Pilar M.

AU - Perez, Jose I.A.

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Schumacher, Fredrick

AU - March, Loic Le

AU - Pharoah, Paul D.P.

AU - Dunning, Alison M.

AU - Shah, Mitul

AU - Luben, Robert

AU - Brown, Judith

AU - Couch, Fergus J.

AU - Wang, Xianshu

AU - Vachon, Celine

AU - Olson, Janet E.

AU - Lambrechts, Diether

AU - Moisse, Matthieu

AU - Paridaens, Robert

AU - Christiaens, Marie Rose

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Laurent-Puig, Pierre

AU - Mulot, Claire

AU - Marme, Frederick

AU - Burwinkel, Barbara

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Tchatchou, Srine

AU - Mulligan, Anna Marie

AU - Dörk, Thilo

AU - Bogdanova, Natalia V.

AU - Antonenkova, Natalia N.

AU - Anton-Culver, Hoda

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Garcia-Closas, Montserrat

AU - Figueroa, Jonine

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Devilee, Peter

AU - Tollenaar, Robert A.E.M.

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J.

AU - Kristensen, Vessela N.

AU - Australian Ovarian Cancer Study Group, Susan Slager

AU - Tol, Ama E.

AU - Ambrosone, Christine B.

AU - Yannoukakos, Drakoulis

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Barile, Monica

AU - Mariani, Paolo

AU - Hooning, Maartje J.

AU - Martens, John W.M.

AU - Margriet Collée, J.

AU - Jager, Agnes

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Giles, Graham G.

AU - McLean, Catriona

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon Dschun

AU - The Genica Network, Hermann Brenner

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Swerdlow, Anthony

AU - Ashworth, Alan

AU - Orr, Nick

AU - Jones, Michael

AU - Simard, Jacques

AU - Goldberg, Mark S.

AU - Labrèche, France

AU - Dumont, Martine

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Mannermaa, Arto

AU - Hamann, Ute

AU - Chenevix-Trench, Georgia

AU - Blomqvist, Carl

AU - Aittomäki, Kristiina

AU - Easton, Douglas F.

AU - Nevanlinna, Heli

PY - 2014/11/12

Y1 - 2014/11/12

N2 - Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% Cl: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01 -1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. This is an open-access article free of all copyright.

AB - Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% Cl: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01 -1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. This is an open-access article free of all copyright.

UR - http://www.scopus.com/inward/record.url?scp=84912002894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84912002894&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0109973

DO - 10.1371/journal.pone.0109973

M3 - Article

C2 - 25390939

AN - SCOPUS:84912002894

SN - 1932-6203

VL - 9

JO - PloS one

JF - PloS one

IS - 11

M1 - e109973

ER -

MicroRNA related polymorphisms and breast cancer risk

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