Genetic predisposition to ductal carcinoma in situ of the breast

Christos Petridis, Mark N. Brook, Vandna Shah, Kelly Kohut, Patricia Gorman, Michele Caneppele, Dina Levi, Efterpi Papouli, Nick Orr, Angela Cox, Simon S. Cross, Isabel dos-Santos-Silva, Julian Peto, Anthony Swerdlow, Minouk J. Schoemaker, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Javier BenitezAnna González-Neira, Daniel C. Tessier, Daniel Vincent, Jingmei Li, Jonine Figueroa, Vessela Kristensen, Anne Lise Borresen-Dale, Penny Soucy, Jacques Simard, Roger L. Milne, Graham G. Giles, Sara Margolin, Annika Lindblom, Thomas Brüning, Hiltrud Brauch, Melissa C. Southey, John L. Hopper, Thilo Dörk, Natalia V. Bogdanova, Maria Kabisch, Ute Hamann, Rita K. Schmutzler, Alfons Meindl, Hermann Brenner, Volker Arndt, Robert Winqvist, Katri Pylkäs, Peter A. Fasching, Matthias W. Beckmann, Jan Lubinski, Anna Jakubowska, Anna Marie Mulligan, Irene L. Andrulis, Rob A E M Tollenaar, Peter Devilee, Loic Le Marchand, Christopher A. Haiman, Arto Mannermaa, Veli Matti Kosma, Paolo Radice, Paolo Peterlongo, Frederik Marme, Barbara Burwinkel, Carolien H M van Deurzen, Antoinette Hollestelle, Nicola Miller, Michael J. Kerin, Diether Lambrechts, Giuseppe Floris, Jelle Wesseling, Henrik Flyger, Stig E. Bojesen, Song Yao, Christine B. Ambrosone, Georgia Chenevix-Trench, Thérèse Truong, Pascal Guénel, Anja Rudolph, Jenny Chang-Claude, Heli Nevanlinna, Carl Blomqvist, Kamila Czene, Judith S. Brand, Janet E Olson, Fergus J Couch, Alison M. Dunning, Per Hall, Douglas F. Easton, Paul D P Pharoah, Sarah E. Pinder, Marjanka K. Schmidt, Ian Tomlinson, Rebecca Roylance, Montserrat García-Closas, Elinor J. Sawyer

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P <5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

Original languageEnglish (US)
Article number22
JournalBreast Cancer Research
Volume18
Issue number1
DOIs
StatePublished - Feb 17 2016

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Genetic Predisposition to Disease
Ductal Carcinoma
Breast
Estrogen Receptors
Breast Neoplasms
Genetic Polymorphisms
Single Nucleotide Polymorphism

Keywords

  • Association study
  • Common variants
  • Ductal carcinoma in situ
  • Genetic predisposition

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Petridis, C., Brook, M. N., Shah, V., Kohut, K., Gorman, P., Caneppele, M., ... Sawyer, E. J. (2016). Genetic predisposition to ductal carcinoma in situ of the breast. Breast Cancer Research, 18(1), [22]. https://doi.org/10.1186/s13058-016-0675-7

Genetic predisposition to ductal carcinoma in situ of the breast. / Petridis, Christos; Brook, Mark N.; Shah, Vandna; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Levi, Dina; Papouli, Efterpi; Orr, Nick; Cox, Angela; Cross, Simon S.; dos-Santos-Silva, Isabel; Peto, Julian; Swerdlow, Anthony; Schoemaker, Minouk J.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Benitez, Javier; González-Neira, Anna; Tessier, Daniel C.; Vincent, Daniel; Li, Jingmei; Figueroa, Jonine; Kristensen, Vessela; Borresen-Dale, Anne Lise; Soucy, Penny; Simard, Jacques; Milne, Roger L.; Giles, Graham G.; Margolin, Sara; Lindblom, Annika; Brüning, Thomas; Brauch, Hiltrud; Southey, Melissa C.; Hopper, John L.; Dörk, Thilo; Bogdanova, Natalia V.; Kabisch, Maria; Hamann, Ute; Schmutzler, Rita K.; Meindl, Alfons; Brenner, Hermann; Arndt, Volker; Winqvist, Robert; Pylkäs, Katri; Fasching, Peter A.; Beckmann, Matthias W.; Lubinski, Jan; Jakubowska, Anna; Mulligan, Anna Marie; Andrulis, Irene L.; Tollenaar, Rob A E M; Devilee, Peter; Le Marchand, Loic; Haiman, Christopher A.; Mannermaa, Arto; Kosma, Veli Matti; Radice, Paolo; Peterlongo, Paolo; Marme, Frederik; Burwinkel, Barbara; van Deurzen, Carolien H M; Hollestelle, Antoinette; Miller, Nicola; Kerin, Michael J.; Lambrechts, Diether; Floris, Giuseppe; Wesseling, Jelle; Flyger, Henrik; Bojesen, Stig E.; Yao, Song; Ambrosone, Christine B.; Chenevix-Trench, Georgia; Truong, Thérèse; Guénel, Pascal; Rudolph, Anja; Chang-Claude, Jenny; Nevanlinna, Heli; Blomqvist, Carl; Czene, Kamila; Brand, Judith S.; Olson, Janet E; Couch, Fergus J; Dunning, Alison M.; Hall, Per; Easton, Douglas F.; Pharoah, Paul D P; Pinder, Sarah E.; Schmidt, Marjanka K.; Tomlinson, Ian; Roylance, Rebecca; García-Closas, Montserrat; Sawyer, Elinor J.

In: Breast Cancer Research, Vol. 18, No. 1, 22, 17.02.2016.

Research output: Contribution to journalArticle

Petridis, C, Brook, MN, Shah, V, Kohut, K, Gorman, P, Caneppele, M, Levi, D, Papouli, E, Orr, N, Cox, A, Cross, SS, dos-Santos-Silva, I, Peto, J, Swerdlow, A, Schoemaker, MJ, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Benitez, J, González-Neira, A, Tessier, DC, Vincent, D, Li, J, Figueroa, J, Kristensen, V, Borresen-Dale, AL, Soucy, P, Simard, J, Milne, RL, Giles, GG, Margolin, S, Lindblom, A, Brüning, T, Brauch, H, Southey, MC, Hopper, JL, Dörk, T, Bogdanova, NV, Kabisch, M, Hamann, U, Schmutzler, RK, Meindl, A, Brenner, H, Arndt, V, Winqvist, R, Pylkäs, K, Fasching, PA, Beckmann, MW, Lubinski, J, Jakubowska, A, Mulligan, AM, Andrulis, IL, Tollenaar, RAEM, Devilee, P, Le Marchand, L, Haiman, CA, Mannermaa, A, Kosma, VM, Radice, P, Peterlongo, P, Marme, F, Burwinkel, B, van Deurzen, CHM, Hollestelle, A, Miller, N, Kerin, MJ, Lambrechts, D, Floris, G, Wesseling, J, Flyger, H, Bojesen, SE, Yao, S, Ambrosone, CB, Chenevix-Trench, G, Truong, T, Guénel, P, Rudolph, A, Chang-Claude, J, Nevanlinna, H, Blomqvist, C, Czene, K, Brand, JS, Olson, JE, Couch, FJ, Dunning, AM, Hall, P, Easton, DF, Pharoah, PDP, Pinder, SE, Schmidt, MK, Tomlinson, I, Roylance, R, García-Closas, M & Sawyer, EJ 2016, 'Genetic predisposition to ductal carcinoma in situ of the breast', Breast Cancer Research, vol. 18, no. 1, 22. https://doi.org/10.1186/s13058-016-0675-7
Petridis C, Brook MN, Shah V, Kohut K, Gorman P, Caneppele M et al. Genetic predisposition to ductal carcinoma in situ of the breast. Breast Cancer Research. 2016 Feb 17;18(1). 22. https://doi.org/10.1186/s13058-016-0675-7
Petridis, Christos ; Brook, Mark N. ; Shah, Vandna ; Kohut, Kelly ; Gorman, Patricia ; Caneppele, Michele ; Levi, Dina ; Papouli, Efterpi ; Orr, Nick ; Cox, Angela ; Cross, Simon S. ; dos-Santos-Silva, Isabel ; Peto, Julian ; Swerdlow, Anthony ; Schoemaker, Minouk J. ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Michailidou, Kyriaki ; Benitez, Javier ; González-Neira, Anna ; Tessier, Daniel C. ; Vincent, Daniel ; Li, Jingmei ; Figueroa, Jonine ; Kristensen, Vessela ; Borresen-Dale, Anne Lise ; Soucy, Penny ; Simard, Jacques ; Milne, Roger L. ; Giles, Graham G. ; Margolin, Sara ; Lindblom, Annika ; Brüning, Thomas ; Brauch, Hiltrud ; Southey, Melissa C. ; Hopper, John L. ; Dörk, Thilo ; Bogdanova, Natalia V. ; Kabisch, Maria ; Hamann, Ute ; Schmutzler, Rita K. ; Meindl, Alfons ; Brenner, Hermann ; Arndt, Volker ; Winqvist, Robert ; Pylkäs, Katri ; Fasching, Peter A. ; Beckmann, Matthias W. ; Lubinski, Jan ; Jakubowska, Anna ; Mulligan, Anna Marie ; Andrulis, Irene L. ; Tollenaar, Rob A E M ; Devilee, Peter ; Le Marchand, Loic ; Haiman, Christopher A. ; Mannermaa, Arto ; Kosma, Veli Matti ; Radice, Paolo ; Peterlongo, Paolo ; Marme, Frederik ; Burwinkel, Barbara ; van Deurzen, Carolien H M ; Hollestelle, Antoinette ; Miller, Nicola ; Kerin, Michael J. ; Lambrechts, Diether ; Floris, Giuseppe ; Wesseling, Jelle ; Flyger, Henrik ; Bojesen, Stig E. ; Yao, Song ; Ambrosone, Christine B. ; Chenevix-Trench, Georgia ; Truong, Thérèse ; Guénel, Pascal ; Rudolph, Anja ; Chang-Claude, Jenny ; Nevanlinna, Heli ; Blomqvist, Carl ; Czene, Kamila ; Brand, Judith S. ; Olson, Janet E ; Couch, Fergus J ; Dunning, Alison M. ; Hall, Per ; Easton, Douglas F. ; Pharoah, Paul D P ; Pinder, Sarah E. ; Schmidt, Marjanka K. ; Tomlinson, Ian ; Roylance, Rebecca ; García-Closas, Montserrat ; Sawyer, Elinor J. / Genetic predisposition to ductal carcinoma in situ of the breast. In: Breast Cancer Research. 2016 ; Vol. 18, No. 1.
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title = "Genetic predisposition to ductal carcinoma in situ of the breast",
abstract = "Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 {\%}) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P <5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.",
keywords = "Association study, Common variants, Ductal carcinoma in situ, Genetic predisposition",
author = "Christos Petridis and Brook, {Mark N.} and Vandna Shah and Kelly Kohut and Patricia Gorman and Michele Caneppele and Dina Levi and Efterpi Papouli and Nick Orr and Angela Cox and Cross, {Simon S.} and Isabel dos-Santos-Silva and Julian Peto and Anthony Swerdlow and Schoemaker, {Minouk J.} and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Kyriaki Michailidou and Javier Benitez and Anna Gonz{\'a}lez-Neira and Tessier, {Daniel C.} and Daniel Vincent and Jingmei Li and Jonine Figueroa and Vessela Kristensen and Borresen-Dale, {Anne Lise} and Penny Soucy and Jacques Simard and Milne, {Roger L.} and Giles, {Graham G.} and Sara Margolin and Annika Lindblom and Thomas Br{\"u}ning and Hiltrud Brauch and Southey, {Melissa C.} and Hopper, {John L.} and Thilo D{\"o}rk and Bogdanova, {Natalia V.} and Maria Kabisch and Ute Hamann and Schmutzler, {Rita K.} and Alfons Meindl and Hermann Brenner and Volker Arndt and Robert Winqvist and Katri Pylk{\"a}s and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Jan Lubinski and Anna Jakubowska and Mulligan, {Anna Marie} and Andrulis, {Irene L.} and Tollenaar, {Rob A E M} and Peter Devilee and {Le Marchand}, Loic and Haiman, {Christopher A.} and Arto Mannermaa and Kosma, {Veli Matti} and Paolo Radice and Paolo Peterlongo and Frederik Marme and Barbara Burwinkel and {van Deurzen}, {Carolien H M} and Antoinette Hollestelle and Nicola Miller and Kerin, {Michael J.} and Diether Lambrechts and Giuseppe Floris and Jelle Wesseling and Henrik Flyger and Bojesen, {Stig E.} and Song Yao and Ambrosone, {Christine B.} and Georgia Chenevix-Trench and Th{\'e}r{\`e}se Truong and Pascal Gu{\'e}nel and Anja Rudolph and Jenny Chang-Claude and Heli Nevanlinna and Carl Blomqvist and Kamila Czene and Brand, {Judith S.} and Olson, {Janet E} and Couch, {Fergus J} and Dunning, {Alison M.} and Per Hall and Easton, {Douglas F.} and Pharoah, {Paul D P} and Pinder, {Sarah E.} and Schmidt, {Marjanka K.} and Ian Tomlinson and Rebecca Roylance and Montserrat Garc{\'i}a-Closas and Sawyer, {Elinor J.}",
year = "2016",
month = "2",
day = "17",
doi = "10.1186/s13058-016-0675-7",
language = "English (US)",
volume = "18",
journal = "Breast Cancer Research",
issn = "1465-5411",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Genetic predisposition to ductal carcinoma in situ of the breast

AU - Petridis, Christos

AU - Brook, Mark N.

AU - Shah, Vandna

AU - Kohut, Kelly

AU - Gorman, Patricia

AU - Caneppele, Michele

AU - Levi, Dina

AU - Papouli, Efterpi

AU - Orr, Nick

AU - Cox, Angela

AU - Cross, Simon S.

AU - dos-Santos-Silva, Isabel

AU - Peto, Julian

AU - Swerdlow, Anthony

AU - Schoemaker, Minouk J.

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - Benitez, Javier

AU - González-Neira, Anna

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Li, Jingmei

AU - Figueroa, Jonine

AU - Kristensen, Vessela

AU - Borresen-Dale, Anne Lise

AU - Soucy, Penny

AU - Simard, Jacques

AU - Milne, Roger L.

AU - Giles, Graham G.

AU - Margolin, Sara

AU - Lindblom, Annika

AU - Brüning, Thomas

AU - Brauch, Hiltrud

AU - Southey, Melissa C.

AU - Hopper, John L.

AU - Dörk, Thilo

AU - Bogdanova, Natalia V.

AU - Kabisch, Maria

AU - Hamann, Ute

AU - Schmutzler, Rita K.

AU - Meindl, Alfons

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Mulligan, Anna Marie

AU - Andrulis, Irene L.

AU - Tollenaar, Rob A E M

AU - Devilee, Peter

AU - Le Marchand, Loic

AU - Haiman, Christopher A.

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Marme, Frederik

AU - Burwinkel, Barbara

AU - van Deurzen, Carolien H M

AU - Hollestelle, Antoinette

AU - Miller, Nicola

AU - Kerin, Michael J.

AU - Lambrechts, Diether

AU - Floris, Giuseppe

AU - Wesseling, Jelle

AU - Flyger, Henrik

AU - Bojesen, Stig E.

AU - Yao, Song

AU - Ambrosone, Christine B.

AU - Chenevix-Trench, Georgia

AU - Truong, Thérèse

AU - Guénel, Pascal

AU - Rudolph, Anja

AU - Chang-Claude, Jenny

AU - Nevanlinna, Heli

AU - Blomqvist, Carl

AU - Czene, Kamila

AU - Brand, Judith S.

AU - Olson, Janet E

AU - Couch, Fergus J

AU - Dunning, Alison M.

AU - Hall, Per

AU - Easton, Douglas F.

AU - Pharoah, Paul D P

AU - Pinder, Sarah E.

AU - Schmidt, Marjanka K.

AU - Tomlinson, Ian

AU - Roylance, Rebecca

AU - García-Closas, Montserrat

AU - Sawyer, Elinor J.

PY - 2016/2/17

Y1 - 2016/2/17

N2 - Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P <5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

AB - Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P <5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

KW - Association study

KW - Common variants

KW - Ductal carcinoma in situ

KW - Genetic predisposition

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U2 - 10.1186/s13058-016-0675-7

DO - 10.1186/s13058-016-0675-7

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AN - SCOPUS:84957951400

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

IS - 1

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ER -