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Title: Identification of new genetic susceptibility Loci for breast cancer through consideration of gene-environment interactions
Authors: Schoeps, Anja ×
Rudolph, Anja
Seibold, Petra
Dunning, Alison M
Milne, Roger L
Bojesen, Stig E
Swerdlow, Anthony
Andrulis, Irene
Brenner, Hermann
Behrens, Sabine
Orr, Nicholas
Jones, Michael
Ashworth, Alan
Li, Jingmei
Cramp, Helen
Connley, Dan
Czene, Kamila
Darabi, Hatef
Chanock, Stephen J
Lissowska, Jolanta
Figueroa, Jonine D
Knight, Julia
Glendon, Gord
Mulligan, Anna M
Dumont, Martine
Severi, Gianluca
Baglietto, Laura
Olson, Janet
Vachon, Celine
Purrington, Kristen
Moisse, Matthieu
Neven, Patrick
Wildiers, Hans
Spurdle, Amanda
Kosma, Veli-Matti
Kataja, Vesa
Hartikainen, Jaana M
Hamann, Ute
Ko, Yon-Dschun
Dieffenbach, Aida K
Arndt, Volker
Stegmaier, Christa
Malats, Núria
Arias Perez, José I
Benítez, Javier
Flyger, Henrik
Nordestgaard, Børge G
Truong, Thérèse
Cordina-Duverger, Emilie
Menegaux, Florence
Dos Santos Silva, Isabel
Fletcher, Olivia
Johnson, Nichola
Häberle, Lothar
Beckmann, Matthias W
Ekici, Arif B
Braaf, Linde
Atsma, Femke
van den Broek, Alexandra J
Makalic, Enes
Schmidt, Daniel F
Southey, Melissa C
Cox, Angela
Simard, Jacques
Giles, Graham G
Lambrechts, Diether
Mannermaa, Arto
Brauch, Hiltrud
Guénel, Pascal
Peto, Julian
Fasching, Peter A
Hopper, John
Flesch-Janys, Dieter
Couch, Fergus
Chenevix-Trench, Georgia
Pharoah, Paul D P
Garcia-Closas, Montserrat
Schmidt, Marjanka K
Hall, Per
Easton, Douglas F
Chang-Claude, Jenny #
Issue Date: Jan-2014
Publisher: Wiley-Liss, Inc.
Series Title: Genetic Epidemiology vol:38 issue:1 pages:84-93
Article number: 10.1002/gepi.21771
Abstract: Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07) ), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05) ). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.
ISSN: 0741-0395
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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