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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Genetic Epidemiology |
Vol/bind | 38 |
Udgave nummer | 1 |
Sider (fra-til) | 84-93 |
Antal sider | 10 |
ISSN | 0741-0395 |
DOI | |
Status | Udgivet - jan. 2014 |
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Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions. / 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.
I: Genetic Epidemiology, Bind 38, Nr. 1, 01.2014, s. 84-93.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions
AU - Schoeps, Anja
AU - Rudolph, Anja
AU - Seibold, Petra
AU - Dunning, Alison M
AU - Milne, Roger L
AU - Bojesen, Stig E
AU - Swerdlow, Anthony
AU - Andrulis, Irene
AU - Brenner, Hermann
AU - Behrens, Sabine
AU - Orr, Nicholas
AU - Jones, Michael
AU - Ashworth, Alan
AU - Li, Jingmei
AU - Cramp, Helen
AU - Connley, Dan
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Chanock, Stephen J
AU - Lissowska, Jolanta
AU - Figueroa, Jonine D
AU - Knight, Julia
AU - Glendon, Gord
AU - Mulligan, Anna M
AU - Dumont, Martine
AU - Severi, Gianluca
AU - Baglietto, Laura
AU - Olson, Janet
AU - Vachon, Celine
AU - Purrington, Kristen
AU - Moisse, Matthieu
AU - Neven, Patrick
AU - Wildiers, Hans
AU - Spurdle, Amanda
AU - Kosma, Veli-Matti
AU - Kataja, Vesa
AU - Hartikainen, Jaana M
AU - Hamann, Ute
AU - Ko, Yon-Dschun
AU - Dieffenbach, Aida K
AU - Arndt, Volker
AU - Stegmaier, Christa
AU - Malats, Núria
AU - Arias Perez, José I
AU - Benítez, Javier
AU - Flyger, Henrik
AU - Nordestgaard, Børge G
AU - Truong, Thérèse
AU - Cordina-Duverger, Emilie
AU - Menegaux, Florence
AU - dos Santos Silva, Isabel
AU - Fletcher, Olivia
AU - Johnson, Nichola
AU - Häberle, Lothar
AU - Beckmann, Matthias W
AU - Ekici, Arif B
AU - Braaf, Linde
AU - Atsma, Femke
AU - van den Broek, Alexandra J
AU - Makalic, Enes
AU - Schmidt, Daniel F
AU - Southey, Melissa C
AU - Cox, Angela
AU - Simard, Jacques
AU - Giles, Graham G
AU - Lambrechts, Diether
AU - Mannermaa, Arto
AU - Brauch, Hiltrud
AU - Guénel, Pascal
AU - Peto, Julian
AU - Fasching, Peter A
AU - Hopper, John
AU - Flesch-Janys, Dieter
AU - Couch, Fergus
AU - Chenevix-Trench, Georgia
AU - Pharoah, Paul D P
AU - Garcia-Closas, Montserrat
AU - Schmidt, Marjanka K
AU - Hall, Per
AU - Easton, Douglas F
AU - Chang-Claude, Jenny
N1 - © 2013 WILEY PERIODICALS, INC.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Body Height
KW - Body Mass Index
KW - Breast Neoplasms
KW - Chromosomes, Human, Pair 21
KW - Chromosomes, Human, Pair 6
KW - European Continental Ancestry Group
KW - Female
KW - Gene-Environment Interaction
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Humans
KW - Linkage Disequilibrium
KW - Menarche
KW - Middle Aged
KW - Parity
KW - Polymorphism, Single Nucleotide
KW - Postmenopause
U2 - 10.1002/gepi.21771
DO - 10.1002/gepi.21771
M3 - Journal article
C2 - 24248812
VL - 38
SP - 84
EP - 93
JO - Genetic Epidemiology
JF - Genetic Epidemiology
SN - 0741-0395
IS - 1
ER -