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A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication

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A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication. / Hein, Rebecca; Flesch-Janys, Dieter; Dahmen, Norbert; Beckmann, Lars; Lindström, Sara; Schoof, Nils; Czene, Kamila; Mittelstraß, Kirstin; Illig, Thomas; Seibold, Petra; Behrens, Sabine; Humphreys, Keith; Li, Jingmei; Liu, Jianjun; Olson, Janet E; Wang, Xianshu; Hankinson, Susan E; Truong, Thérèse; Menegaux, Florence; Dos Santos Silva, Isabel; Johnson, Nichola; Chen, Shou-Tung; Yu, Jyh-Cherng; Ziogas, Argyrios; Kataja, Vesa; Kosma, Veli-Matti; Mannermaa, Arto; Anton-Culver, Hoda; Shen, Chen-Yang; Brauch, Hiltrud; Peto, Julian; Guénel, Pascal; Kraft, Peter; Couch, Fergus J; Easton, Douglas F; Hall, Per; Chang-Claude, Jenny; GENICA Network.

In: BREAST CANCER RES TR, Vol. 138, No. 2, 01.04.2013, p. 529-42.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hein, R, Flesch-Janys, D, Dahmen, N, Beckmann, L, Lindström, S, Schoof, N, Czene, K, Mittelstraß, K, Illig, T, Seibold, P, Behrens, S, Humphreys, K, Li, J, Liu, J, Olson, JE, Wang, X, Hankinson, SE, Truong, T, Menegaux, F, Dos Santos Silva, I, Johnson, N, Chen, S-T, Yu, J-C, Ziogas, A, Kataja, V, Kosma, V-M, Mannermaa, A, Anton-Culver, H, Shen, C-Y, Brauch, H, Peto, J, Guénel, P, Kraft, P, Couch, FJ, Easton, DF, Hall, P, Chang-Claude, J & GENICA Network 2013, 'A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication', BREAST CANCER RES TR, vol. 138, no. 2, pp. 529-42. https://doi.org/10.1007/s10549-013-2443-z

APA

Hein, R., Flesch-Janys, D., Dahmen, N., Beckmann, L., Lindström, S., Schoof, N., Czene, K., Mittelstraß, K., Illig, T., Seibold, P., Behrens, S., Humphreys, K., Li, J., Liu, J., Olson, J. E., Wang, X., Hankinson, S. E., Truong, T., Menegaux, F., ... GENICA Network (2013). A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication. BREAST CANCER RES TR, 138(2), 529-42. https://doi.org/10.1007/s10549-013-2443-z

Vancouver

Hein R, Flesch-Janys D, Dahmen N, Beckmann L, Lindström S, Schoof N et al. A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication. BREAST CANCER RES TR. 2013 Apr 1;138(2):529-42. https://doi.org/10.1007/s10549-013-2443-z

Bibtex

@article{7c194991e3e24a76ac00ab75aa1a31fa,
title = "A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication",
abstract = "Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.",
keywords = "Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Case-Control Studies, Chromosomes, Human, Estrogen Replacement Therapy, Estrogens, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Postmenopause, Progestins, Risk Factors, Sequence Analysis, DNA",
author = "Rebecca Hein and Dieter Flesch-Janys and Norbert Dahmen and Lars Beckmann and Sara Lindstr{\"o}m and Nils Schoof and Kamila Czene and Kirstin Mittelstra{\ss} and Thomas Illig and Petra Seibold and Sabine Behrens and Keith Humphreys and Jingmei Li and Jianjun Liu and Olson, {Janet E} and Xianshu Wang and Hankinson, {Susan E} and Th{\'e}r{\`e}se Truong and Florence Menegaux and {Dos Santos Silva}, Isabel and Nichola Johnson and Shou-Tung Chen and Jyh-Cherng Yu and Argyrios Ziogas and Vesa Kataja and Veli-Matti Kosma and Arto Mannermaa and Hoda Anton-Culver and Chen-Yang Shen and Hiltrud Brauch and Julian Peto and Pascal Gu{\'e}nel and Peter Kraft and Couch, {Fergus J} and Easton, {Douglas F} and Per Hall and Jenny Chang-Claude and {GENICA Network} and Volker Harth",
year = "2013",
month = apr,
day = "1",
doi = "10.1007/s10549-013-2443-z",
language = "English",
volume = "138",
pages = "529--42",
journal = "BREAST CANCER RES TR",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",

}

RIS

TY - JOUR

T1 - A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication

AU - Hein, Rebecca

AU - Flesch-Janys, Dieter

AU - Dahmen, Norbert

AU - Beckmann, Lars

AU - Lindström, Sara

AU - Schoof, Nils

AU - Czene, Kamila

AU - Mittelstraß, Kirstin

AU - Illig, Thomas

AU - Seibold, Petra

AU - Behrens, Sabine

AU - Humphreys, Keith

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Olson, Janet E

AU - Wang, Xianshu

AU - Hankinson, Susan E

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Dos Santos Silva, Isabel

AU - Johnson, Nichola

AU - Chen, Shou-Tung

AU - Yu, Jyh-Cherng

AU - Ziogas, Argyrios

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Mannermaa, Arto

AU - Anton-Culver, Hoda

AU - Shen, Chen-Yang

AU - Brauch, Hiltrud

AU - Peto, Julian

AU - Guénel, Pascal

AU - Kraft, Peter

AU - Couch, Fergus J

AU - Easton, Douglas F

AU - Hall, Per

AU - Chang-Claude, Jenny

AU - GENICA Network

AU - Harth, Volker

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.

AB - Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.

KW - Breast Neoplasms

KW - Carcinoma, Ductal, Breast

KW - Carcinoma, Lobular

KW - Case-Control Studies

KW - Chromosomes, Human

KW - Estrogen Replacement Therapy

KW - Estrogens

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Linkage Disequilibrium

KW - Polymorphism, Single Nucleotide

KW - Postmenopause

KW - Progestins

KW - Risk Factors

KW - Sequence Analysis, DNA

U2 - 10.1007/s10549-013-2443-z

DO - 10.1007/s10549-013-2443-z

M3 - SCORING: Journal article

C2 - 23423446

VL - 138

SP - 529

EP - 542

JO - BREAST CANCER RES TR

JF - BREAST CANCER RES TR

SN - 0167-6806

IS - 2

ER -