A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication

• Published in: Breast cancer research and treatment 2013-04, Vol.138 (2), p.529-542
• Main Authors: Hein, Rebecca, Flesch-Janys, Dieter, Dahmen, Norbert, Beckmann, Lars, Lindström, Sara, Schoof, Nils, Czene, Kamila, Mittelstraß, Kirstin, Illig, Thomas, Seibold, Petra, Behrens, Sabine, Humphreys, Keith, Li, Jingmei, Liu, Jianjun, Olson, Janet E., Wang, Xianshu, Hankinson, Susan E., Truong, Thérèse, Menegaux, Florence, dos Santos Silva, Isabel, Johnson, Nichola, Chen, Shou-Tung, Yu, Jyh-Cherng, Ziogas, Argyrios, Kataja, Vesa, Kosma, Veli-Matti, Mannermaa, Arto, Anton-Culver, Hoda, Shen, Chen-Yang, Brauch, Hiltrud, Peto, Julian, Guénel, Pascal, Kraft, Peter, Couch, Fergus J., Easton, Douglas F., Hall, Per, Chang-Claude, Jenny
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Breast cancer; Breast Neoplasms - chemically induced; Breast Neoplasms - genetics; Cancer; Cancer och onkologi; Cancer research; Cancer therapies; Carcinoma, Ductal, Breast - chemically induced; Carcinoma, Ductal, Breast - genetics; Carcinoma, Lobular - chemically induced; Carcinoma, Lobular - genetics; Care and treatment; Case-Control Studies; Chromosomes; Chromosomes, Human; Disease susceptibility; Epidemiology; Estrogen Replacement Therapy - adverse effects; Estrogens - adverse effects; Female; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genomics; Gynecology. Andrology. Obstetrics; Health aspects; Hormone replacement therapy; Humans; Klinisk medicin; Linkage Disequilibrium; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Menopause; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Oncology, Experimental; Polymorphism, Single Nucleotide; Postmenopausal women; Postmenopause; Progestins - adverse effects; Risk Factors; Sequence Analysis, DNA; Tumors
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-013-2443-z

Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values