Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Schoeps A., Rudolph A., Seibold P., Dunning A.M., Milne R.L., Bojesen S.E., Swerdlow A., Andrulis I., Brenner H., Behrens S., Orr N., Jones M., Ashworth A., Li J., Cramp H., Connley D., Czene K., Darabi H., Chanock S.J., Lissowska J., Figueroa J.D., Knight J., Glendon G., Mulligan A.M., Dumont M., Severi G., Baglietto L., Olson J., Vachon C., Purrington K., Moisse M., Neven P., Wildiers H., Spurdle A., Kosma V.-M., Kataja V., Hartikainen J.M., Hamann U., Ko Y.-D., Dieffenbach A.K., Arndt V., Stegmaier C., Malats N., Arias Perez J.I., Benitez J., Flyger H., Nordestgaard B.G., Truong T., Cordina-Duverger E., Menegaux F., dos Santos Silva I., Fletcher O., Johnson N., Haberle L., Beckmann M.W., Ekici A.B., Braaf L., Atsma F., van den Broek A.J., Makalic E., Schmidt D.F., Southey M.C., Cox A., Simard J., Giles G.G., Lambrechts D., Mannermaa A., Brauch H., Guenel P., Peto J., Fasching P.A., Hopper J., Flesch-Janys D., Couch F., Chenevix-Trench G., Pharoah P.D.P., Garcia-Closas M., Schmidt M.K., Hall P., Easton D.F. and Chang-Claude J. (2014) Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions. Genetic Epidemiology, 38 1: 84-93. doi:10.1002/gepi.21771

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Author Schoeps A.
Rudolph A.
Seibold P.
Dunning A.M.
Milne R.L.
Bojesen S.E.
Swerdlow A.
Andrulis I.
Brenner H.
Behrens S.
Orr N.
Jones M.
Ashworth A.
Li J.
Cramp H.
Connley D.
Czene K.
Darabi H.
Chanock S.J.
Lissowska J.
Figueroa J.D.
Knight J.
Glendon G.
Mulligan A.M.
Dumont M.
Severi G.
Baglietto L.
Olson J.
Vachon C.
Purrington K.
Moisse M.
Neven P.
Wildiers H.
Spurdle A.
Kosma V.-M.
Kataja V.
Hartikainen J.M.
Hamann U.
Ko Y.-D.
Dieffenbach A.K.
Arndt V.
Stegmaier C.
Malats N.
Arias Perez J.I.
Benitez J.
Flyger H.
Nordestgaard B.G.
Truong T.
Cordina-Duverger E.
Menegaux F.
dos Santos Silva I.
Fletcher O.
Johnson N.
Haberle L.
Beckmann M.W.
Ekici A.B.
Braaf L.
Atsma F.
van den Broek A.J.
Makalic E.
Schmidt D.F.
Southey M.C.
Cox A.
Simard J.
Giles G.G.
Lambrechts D.
Mannermaa A.
Brauch H.
Guenel P.
Peto J.
Fasching P.A.
Hopper J.
Flesch-Janys D.
Couch F.
Chenevix-Trench G.
Pharoah P.D.P.
Garcia-Closas M.
Schmidt M.K.
Hall P.
Easton D.F.
Chang-Claude J.
Title Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions
Journal name Genetic Epidemiology   Check publisher's open access policy
ISSN 0741-0395
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1002/gepi.21771
Open Access Status Not yet assessed
Volume 38
Issue 1
Start page 84
End page 93
Total pages 10
Place of publication Hoboken, NJ, U.S.A.
Publisher Jossey Bass, Ed. & Pub.
Language eng
Subject 2716 Genetics (clinical)
2713 Epidemiology
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/m2 (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m2 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.
Keyword Body mass index
Breast cancer risk
Case-control study
Gene-environment interaction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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Created: Wed, 02 Apr 2014, 00:45:30 EST by Matthew Lamb on behalf of School of Medicine