Rudolph, Anja, Hein, Rebecca, Lindstroem, Sara, Beckmann, Lars, Behrens, Sabine, Liu, Jianjun ORCID: 0000-0002-3255-3019, Aschard, Hugues, Bolla, Manjeet K., Wang, Jean, Truong, Therese, Cordina-Duverger, Emilie, Menegaux, Florence ORCID: 0000-0003-3363-6411, Bruening, Thomas, Harth, Volker, Severi, Gianluca ORCID: 0000-0001-7157-419X, Baglietto, Laura ORCID: 0000-0002-8193-7529, Southey, Melissa ORCID: 0000-0002-6313-9005, Chanock, Stephen J., Lissowska, Jolanta ORCID: 0000-0003-2695-5799, 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 ORCID: 0000-0002-7239-5297, Ashworth, Alan, Orr, Nicholas, Schoemaker, Minouk ORCID: 0000-0001-8403-2234, Webb, Penny M., Guenel, Pascal ORCID: 0000-0002-8359-518X, Brauch, Hiltrud ORCID: 0000-0001-7531-2736, Giles, Graham ORCID: 0000-0003-4946-9099, Garcia-Closas, Montserrat ORCID: 0000-0003-1033-2650, Czene, Kamila ORCID: 0000-0002-3233-5695, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Couch, Fergus J., Andrulis, Irene L., Swerdlow, Anthony ORCID: 0000-0001-5550-4159, Hunter, David J., Flesch-Janys, Dieter, Easton, Douglas F., Hall, Per, Nevanlinna, Heli ORCID: 0000-0002-0916-2976, Kraft, Peter and Chang-Claude, Jenny (2013). Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study. Endocr.-Relat. Cancer, 20 (6). S. 875 - 888. BRISTOL: BIOSCIENTIFICA LTD. ISSN 1479-6821

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Abstract

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 x 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 P-int <= 8.9 x 10(-6)), two SNPs in SLC25A21 (combined P-int <= 4.8 x 10(-5)), and three SNPs in PLCG2 (combined P-int <= 4.5 x 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined P-int <= 2.7 x 10(-5)), one SNP in CD80 (combined P-int <= 8.2 x 10(-6)), three SNPs on chr17 near TMEM132E (combined P-int <= 2.2 x 10(-6)), and two SNPs on chr18 near SLC25A52 (combined P-int <= 4.6 x 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rudolph, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hein, RebeccaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindstroem, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrens, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, JianjunUNSPECIFIEDorcid.org/0000-0002-3255-3019UNSPECIFIED
Aschard, HuguesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JeanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truong, ThereseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cordina-Duverger, EmilieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menegaux, FlorenceUNSPECIFIEDorcid.org/0000-0003-3363-6411UNSPECIFIED
Bruening, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Harth, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Severi, GianlucaUNSPECIFIEDorcid.org/0000-0001-7157-419XUNSPECIFIED
Baglietto, LauraUNSPECIFIEDorcid.org/0000-0002-8193-7529UNSPECIFIED
Southey, MelissaUNSPECIFIEDorcid.org/0000-0002-6313-9005UNSPECIFIED
Chanock, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lissowska, JolantaUNSPECIFIEDorcid.org/0000-0003-2695-5799UNSPECIFIED
Figueroa, Jonine D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, MikaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Humpreys, KeithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Darabi, HatefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olson, Janet E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stevens, Kristen N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vachon, Celine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knight, Julia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glendon, GordUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mulligan, Anna MarieUNSPECIFIEDorcid.org/0000-0002-7239-5297UNSPECIFIED
Ashworth, AlanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orr, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoemaker, MinoukUNSPECIFIEDorcid.org/0000-0001-8403-2234UNSPECIFIED
Webb, Penny M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, PascalUNSPECIFIEDorcid.org/0000-0002-8359-518XUNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Giles, GrahamUNSPECIFIEDorcid.org/0000-0003-4946-9099UNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDorcid.org/0000-0003-1033-2650UNSPECIFIED
Czene, KamilaUNSPECIFIEDorcid.org/0000-0002-3233-5695UNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swerdlow, AnthonyUNSPECIFIEDorcid.org/0000-0001-5550-4159UNSPECIFIED
Hunter, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flesch-Janys, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDorcid.org/0000-0002-0916-2976UNSPECIFIED
Kraft, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-471417
DOI: 10.1530/ERC-13-0349
Journal or Publication Title: Endocr.-Relat. Cancer
Volume: 20
Number: 6
Page Range: S. 875 - 888
Date: 2013
Publisher: BIOSCIENTIFICA LTD
Place of Publication: BRISTOL
ISSN: 1479-6821
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENVIRONMENT INTERACTIONS; PHOSPHOLIPASE C-GAMMA-2; ASSOCIATION; SUSCEPTIBILITY; FGFR2; POLYMORPHISMS; METAANALYSIS; RECEPTORS; NUTRITION; HAPLOTYPEMultiple languages
Oncology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47141

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