Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study
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Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study. / Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J; Lissowska, Jolanta; Figueroa, Jonine D; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E; Stevens, Kristen N; Vachon, Celine M; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J; Andrulis, Irene L; Swerdlow, Anthony; Hunter, David J; Flesch-Janys, Dieter; Easton, Douglas F; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny; GENICA Network ; KConFab Investigators ; AOCS Management Grp ; Breast Canc Association Consortium .
in: ENDOCR-RELAT CANCER, Jahrgang 20, Nr. 6, 01.12.2013, S. 875-87.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study
AU - Rudolph, Anja
AU - Hein, Rebecca
AU - Lindström, Sara
AU - Beckmann, Lars
AU - Behrens, Sabine
AU - Liu, Jianjun
AU - Aschard, Hugues
AU - Bolla, Manjeet K
AU - Wang, Jean
AU - Truong, Thérèse
AU - Cordina-Duverger, Emilie
AU - Menegaux, Florence
AU - Brüning, Thomas
AU - Harth, Volker
AU - Severi, Gianluca
AU - Baglietto, Laura
AU - Southey, Melissa
AU - Chanock, Stephen J
AU - Lissowska, Jolanta
AU - Figueroa, Jonine D
AU - Eriksson, Mikael
AU - Humpreys, Keith
AU - Darabi, Hatef
AU - Olson, Janet E
AU - Stevens, Kristen N
AU - Vachon, Celine M
AU - Knight, Julia A
AU - Glendon, Gord
AU - Mulligan, Anna Marie
AU - Ashworth, Alan
AU - Orr, Nicholas
AU - Schoemaker, Minouk
AU - Webb, Penny M
AU - Guénel, Pascal
AU - Brauch, Hiltrud
AU - Giles, Graham
AU - García-Closas, Montserrat
AU - Czene, Kamila
AU - Chenevix-Trench, Georgia
AU - Couch, Fergus J
AU - Andrulis, Irene L
AU - Swerdlow, Anthony
AU - Hunter, David J
AU - Flesch-Janys, Dieter
AU - Easton, Douglas F
AU - Hall, Per
AU - Nevanlinna, Heli
AU - Kraft, Peter
AU - Chang-Claude, Jenny
AU - GENICA Network ; KConFab Investigators ; AOCS Management Grp ; Breast Canc Association Consortium
PY - 2013/12/1
Y1 - 2013/12/1
N2 - Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.
AB - Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.
U2 - 10.1530/ERC-13-0349
DO - 10.1530/ERC-13-0349
M3 - SCORING: Journal article
C2 - 24080446
VL - 20
SP - 875
EP - 887
JO - ENDOCR-RELAT CANCER
JF - ENDOCR-RELAT CANCER
SN - 1351-0088
IS - 6
ER -