Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

Zhiguo Zhao; Wanqing Wen; Kyriaki Michailidou; Manjeet K. Bolla; Qin Wang; Ben Zhang; Jirong Long; Xiao Ou Shu; Marjanka K. Schmidt; Roger L. Milne; Montserrat García-Closas; Jenny Chang-Claude; Sara Lindstrom; Stig E. Bojesen; Habibul Ahsan; Kristiina Aittomäki; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; Matthias W. Beckmann; Alicia Beeghly-Fadiel; Javier Benitez; Carl Blomqvist; Natalia V. Bogdanova; Anne Lise Børresen-Dale; Judith Brand; Hiltrud Brauch; Hermann Brenner; Barbara Burwinkel; Qiuyin Cai; Graham Casey; Georgia Chenevix-Trench; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Thilo Dörk; Martine Dumont; Peter A. Fasching; Jonine Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Henrik Flyger; Florentia Fostira; Marilie Gammon; Graham G. Giles; Pascal Guénel; Christopher A. Haiman; Ute Hamann; Patricia Harrington; Mikael Hartman; Maartje J. Hooning; John L. Hopper; Anna Jakubowska; Farzana Jasmine; Esther M. John; Nichola Johnson; Maria Kabisch; Sofia Khan; Muhammad Kibriya; Julia A. Knight; Veli Matti Kosma; Mieke Kriege; Vessela Kristensen; Loic Le Marchand; Eunjung Lee; Jingmei Li; Annika Lindblom; Artitaya Lophatananon; Robert Luben; Jan Lubinski; Kathleen E. Malone; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; Frederik Marme; Catriona McLean; Hanne Meijers-Heijboer; Alfons Meindl; Hui Miao; Kenneth Muir; Susan L. Neuhausen; Heli Nevanlinna; Patrick Neven; Janet E. Olson; Barbara Perkins; Paolo Peterlongo; Kelly Anne Phillips; Katri Pylkäs; Anja Rudolph; Regina Santella; Elinor J. Sawyer; Rita K. Schmutzler; Minouk Schoemaker; Mitul Shah; Martha Shrubsole; Melissa C. Southey; Anthony J. Swerdlow; Amanda E. Toland; Ian Tomlinson; Diana Torres; Thérèse Truong; Giske Ursin; Rob B. Van Der Luijt; Senno Verhoef; Shan Wang-Gohrke; Alice S. Whittemore; Robert Winqvist; M. Pilar Zamora; Hui Zhao; Alison M. Dunning; Jacques Simard; Per Hall; Peter Kraft; Paul Pharoah; David Hunter; Douglas F. Easton; Wei Zheng

doi:10.1007/s10552-016-0741-6

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

Zhiguo Zhao, Wanqing Wen, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Ben Zhang, Jirong Long, Xiao Ou Shu, Marjanka K. Schmidt, Roger L. Milne, Montserrat García-Closas, Jenny Chang-Claude, Sara Lindstrom, Stig E. Bojesen, Habibul Ahsan, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Matthias W. BeckmannAlicia Beeghly-Fadiel, Javier Benitez, Carl Blomqvist, Natalia V. Bogdanova, Anne Lise Børresen-Dale, Judith Brand, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Qiuyin Cai, Graham Casey, Georgia Chenevix-Trench, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Thilo Dörk, Martine Dumont, Peter A. Fasching, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Marilie Gammon, Graham G. Giles, Pascal Guénel, Christopher A. Haiman, Ute Hamann, Patricia Harrington, Mikael Hartman, Maartje J. Hooning, John L. Hopper, Anna Jakubowska, Farzana Jasmine, Esther M. John, Nichola Johnson, Maria Kabisch, Sofia Khan, Muhammad Kibriya, Julia A. Knight, Veli Matti Kosma, Mieke Kriege, Vessela Kristensen, Loic Le Marchand, Eunjung Lee, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Robert Luben, Jan Lubinski, Kathleen E. Malone, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Frederik Marme, Catriona McLean, Hanne Meijers-Heijboer, Alfons Meindl, Hui Miao, Kenneth Muir, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, Janet E. Olson, Barbara Perkins, Paolo Peterlongo, Kelly Anne Phillips, Katri Pylkäs, Anja Rudolph, Regina Santella, Elinor J. Sawyer, Rita K. Schmutzler, Minouk Schoemaker, Mitul Shah, Martha Shrubsole, Melissa C. Southey, Anthony J. Swerdlow, Amanda E. Toland, Ian Tomlinson, Diana Torres, Thérèse Truong, Giske Ursin, Rob B. Van Der Luijt, Senno Verhoef, Shan Wang-Gohrke, Alice S. Whittemore, Robert Winqvist, M. Pilar Zamora, Hui Zhao, Alison M. Dunning, Jacques Simard, Per Hall, Peter Kraft, Paul Pharoah, David Hunter, Douglas F. Easton, Wei Zheng

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

14 Scopus citations

Abstract

Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04). Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

Original language	English (US)
Pages (from-to)	679-693
Number of pages	15
Journal	Cancer Causes and Control
Volume	27
Issue number	5
DOIs	https://doi.org/10.1007/s10552-016-0741-6
State	Published - May 1 2016

Keywords

Breast cancer
Epidemiology
GWAS
Genetic susceptibility
Type 2 diabetes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1007/s10552-016-0741-6

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Zhao, Z., Wen, W., Michailidou, K., Bolla, M. K., Wang, Q., Zhang, B., Long, J., Shu, X. O., Schmidt, M. K., Milne, R. L., García-Closas, M., Chang-Claude, J., Lindstrom, S., Bojesen, S. E., Ahsan, H., Aittomäki, K., Andrulis, I. L., Anton-Culver, H., Arndt, V., ... Zheng, W. (2016). Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes and Control, 27(5), 679-693. https://doi.org/10.1007/s10552-016-0741-6

Zhao, Z, Wen, W, Michailidou, K, Bolla, MK, Wang, Q, Zhang, B, Long, J, Shu, XO, Schmidt, MK, Milne, RL, García-Closas, M, Chang-Claude, J, Lindstrom, S, Bojesen, SE, Ahsan, H, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Blomqvist, C, Bogdanova, NV, Børresen-Dale, AL, Brand, J, Brauch, H, Brenner, H, Burwinkel, B, Cai, Q, Casey, G, Chenevix-Trench, G, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dörk, T, Dumont, M, Fasching, PA, Figueroa, J, Flesch-Janys, D, Fletcher, O, Flyger, H, Fostira, F, Gammon, M, Giles, GG, Guénel, P, Haiman, CA, Hamann, U, Harrington, P, Hartman, M, Hooning, MJ, Hopper, JL, Jakubowska, A, Jasmine, F, John, EM, Johnson, N, Kabisch, M, Khan, S, Kibriya, M, Knight, JA, Kosma, VM, Kriege, M, Kristensen, V, Le Marchand, L, Lee, E, Li, J, Lindblom, A, Lophatananon, A, Luben, R, Lubinski, J, Malone, KE, Mannermaa, A, Manoukian, S, Margolin, S, Marme, F, McLean, C, Meijers-Heijboer, H, Meindl, A, Miao, H, Muir, K, Neuhausen, SL, Nevanlinna, H, Neven, P, Olson, JE, Perkins, B, Peterlongo, P, Phillips, KA, Pylkäs, K, Rudolph, A, Santella, R, Sawyer, EJ, Schmutzler, RK, Schoemaker, M, Shah, M, Shrubsole, M, Southey, MC, Swerdlow, AJ, Toland, AE, Tomlinson, I, Torres, D, Truong, T, Ursin, G, Van Der Luijt, RB, Verhoef, S, Wang-Gohrke, S, Whittemore, AS, Winqvist, R, Pilar Zamora, M, Zhao, H, Dunning, AM, Simard, J, Hall, P, Kraft, P, Pharoah, P, Hunter, D, Easton, DF & Zheng, W 2016, 'Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry', Cancer Causes and Control, vol. 27, no. 5, pp. 679-693. https://doi.org/10.1007/s10552-016-0741-6

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title = "Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry",

abstract = "Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04). Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.",

keywords = "Breast cancer, Epidemiology, GWAS, Genetic susceptibility, Type 2 diabetes",

author = "Zhiguo Zhao and Wanqing Wen and Kyriaki Michailidou and Bolla, {Manjeet K.} and Qin Wang and Ben Zhang and Jirong Long and Shu, {Xiao Ou} and Schmidt, {Marjanka K.} and Milne, {Roger L.} and Montserrat Garc{\'i}a-Closas and Jenny Chang-Claude and Sara Lindstrom and Bojesen, {Stig E.} and Habibul Ahsan and Kristiina Aittom{\"a}ki and Andrulis, {Irene L.} and Hoda Anton-Culver and Volker Arndt and Beckmann, {Matthias W.} and Alicia Beeghly-Fadiel and Javier Benitez and Carl Blomqvist and Bogdanova, {Natalia V.} and B{\o}rresen-Dale, {Anne Lise} and Judith Brand and Hiltrud Brauch and Hermann Brenner and Barbara Burwinkel and Qiuyin Cai and Graham Casey and Georgia Chenevix-Trench and Couch, {Fergus J.} and Angela Cox and Cross, {Simon S.} and Kamila Czene and Thilo D{\"o}rk and Martine Dumont and Fasching, {Peter A.} and Jonine Figueroa and Dieter Flesch-Janys and Olivia Fletcher and Henrik Flyger and Florentia Fostira and Marilie Gammon and Giles, {Graham G.} and Pascal Gu{\'e}nel and Haiman, {Christopher A.} and Ute Hamann and Patricia Harrington and Mikael Hartman and Hooning, {Maartje J.} and Hopper, {John L.} and Anna Jakubowska and Farzana Jasmine and John, {Esther M.} and Nichola Johnson and Maria Kabisch and Sofia Khan and Muhammad Kibriya and Knight, {Julia A.} and Kosma, {Veli Matti} and Mieke Kriege and Vessela Kristensen and {Le Marchand}, Loic and Eunjung Lee and Jingmei Li and Annika Lindblom and Artitaya Lophatananon and Robert Luben and Jan Lubinski and Malone, {Kathleen E.} and Arto Mannermaa and Siranoush Manoukian and Sara Margolin and Frederik Marme and Catriona McLean and Hanne Meijers-Heijboer and Alfons Meindl and Hui Miao and Kenneth Muir and Neuhausen, {Susan L.} and Heli Nevanlinna and Patrick Neven and Olson, {Janet E.} and Barbara Perkins and Paolo Peterlongo and Phillips, {Kelly Anne} and Katri Pylk{\"a}s and Anja Rudolph and Regina Santella and Sawyer, {Elinor J.} and Schmutzler, {Rita K.} and Minouk Schoemaker and Mitul Shah and Martha Shrubsole and Southey, {Melissa C.} and Swerdlow, {Anthony J.} and Toland, {Amanda E.} and Ian Tomlinson and Diana Torres and Th{\'e}r{\`e}se Truong and Giske Ursin and {Van Der Luijt}, {Rob B.} and Senno Verhoef and Shan Wang-Gohrke and Whittemore, {Alice S.} and Robert Winqvist and {Pilar Zamora}, M. and Hui Zhao and Dunning, {Alison M.} and Jacques Simard and Per Hall and Peter Kraft and Paul Pharoah and David Hunter and Easton, {Douglas F.} and Wei Zheng",

note = "Publisher Copyright: {\textcopyright} 2016, Springer International Publishing Switzerland.",

year = "2016",

month = may,

day = "1",

doi = "10.1007/s10552-016-0741-6",

language = "English (US)",

volume = "27",

pages = "679--693",

journal = "Cancer Causes and Control",

issn = "0957-5243",

publisher = "Springer Netherlands",

number = "5",

}

TY - JOUR

T1 - Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

AU - Zhao, Zhiguo

AU - Wen, Wanqing

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Zhang, Ben

AU - Long, Jirong

AU - Shu, Xiao Ou

AU - Schmidt, Marjanka K.

AU - Milne, Roger L.

AU - García-Closas, Montserrat

AU - Chang-Claude, Jenny

AU - Lindstrom, Sara

AU - Bojesen, Stig E.

AU - Ahsan, Habibul

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Beckmann, Matthias W.

AU - Beeghly-Fadiel, Alicia

AU - Benitez, Javier

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Børresen-Dale, Anne Lise

AU - Brand, Judith

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Burwinkel, Barbara

AU - Cai, Qiuyin

AU - Casey, Graham

AU - Chenevix-Trench, Georgia

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Czene, Kamila

AU - Dörk, Thilo

AU - Dumont, Martine

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Flyger, Henrik

AU - Fostira, Florentia

AU - Gammon, Marilie

AU - Giles, Graham G.

AU - Guénel, Pascal

AU - Haiman, Christopher A.

AU - Hamann, Ute

AU - Harrington, Patricia

AU - Hartman, Mikael

AU - Hooning, Maartje J.

AU - Hopper, John L.

AU - Jakubowska, Anna

AU - Jasmine, Farzana

AU - John, Esther M.

AU - Johnson, Nichola

AU - Kabisch, Maria

AU - Khan, Sofia

AU - Kibriya, Muhammad

AU - Knight, Julia A.

AU - Kosma, Veli Matti

AU - Kriege, Mieke

AU - Kristensen, Vessela

AU - Le Marchand, Loic

AU - Lee, Eunjung

AU - Li, Jingmei

AU - Lindblom, Annika

AU - Lophatananon, Artitaya

AU - Luben, Robert

AU - Lubinski, Jan

AU - Malone, Kathleen E.

AU - Mannermaa, Arto

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Marme, Frederik

AU - McLean, Catriona

AU - Meijers-Heijboer, Hanne

AU - Meindl, Alfons

AU - Miao, Hui

AU - Muir, Kenneth

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Neven, Patrick

AU - Olson, Janet E.

AU - Perkins, Barbara

AU - Peterlongo, Paolo

AU - Phillips, Kelly Anne

AU - Pylkäs, Katri

AU - Rudolph, Anja

AU - Santella, Regina

AU - Sawyer, Elinor J.

AU - Schmutzler, Rita K.

AU - Schoemaker, Minouk

AU - Shah, Mitul

AU - Shrubsole, Martha

AU - Southey, Melissa C.

AU - Swerdlow, Anthony J.

AU - Toland, Amanda E.

AU - Tomlinson, Ian

AU - Torres, Diana

AU - Truong, Thérèse

AU - Ursin, Giske

AU - Van Der Luijt, Rob B.

AU - Verhoef, Senno

AU - Wang-Gohrke, Shan

AU - Whittemore, Alice S.

AU - Winqvist, Robert

AU - Pilar Zamora, M.

AU - Zhao, Hui

AU - Dunning, Alison M.

AU - Simard, Jacques

AU - Hall, Per

AU - Kraft, Peter

AU - Pharoah, Paul

AU - Hunter, David

AU - Easton, Douglas F.

AU - Zheng, Wei

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04). Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

AB - Purpose: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results: The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p < 0.001), rs9939609 (FTO) (OR 0.94, 95 % CI = 0.92–0.95, p = 4.13E−13), rs7903146 (TCF7L2) (OR 1.04, 95 % CI = 1.02–1.06, p = 1.26E−05), and rs8042680 (PRC1) (OR 0.97, 95 % CI = 0.95–0.99, p = 8.05E−04). Conclusions: We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.

KW - Breast cancer

KW - Epidemiology

KW - GWAS

KW - Genetic susceptibility

KW - Type 2 diabetes

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UR - http://www.scopus.com/inward/citedby.url?scp=84962776158&partnerID=8YFLogxK

U2 - 10.1007/s10552-016-0741-6

DO - 10.1007/s10552-016-0741-6

M3 - Article

C2 - 27053251

AN - SCOPUS:84962776158

SN - 0957-5243

VL - 27

SP - 679

EP - 693

JO - Cancer Causes and Control

JF - Cancer Causes and Control

IS - 5

ER -

Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

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