Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer

• Published in: Nature genetics Vol. 39; no. 7; pp. 865 - 869
• Main Authors: Stacey, Simon N, Stefansson, Kari, Manolescu, Andrei, Sulem, Patrick, Rafnar, Thorunn, Gudmundsson, Julius, Gudjonsson, Sigurjon A, Masson, Gisli, Jakobsdottir, Margret, Thorlacius, Steinunn, Helgason, Agnar, Aben, Katja K, Strobbe, Luc J, Albers-Akkers, Marjo T, Swinkels, Dorine W, Henderson, Brian E, Kolonel, Laurence N, Le Marchand, Loic, Millastre, Esther, Andres, Raquel, Godino, Javier, Garcia-Prats, Maria Dolores, Polo, Eduardo, Tres, Alejandro, Mouy, Magali, Saemundsdottir, Jona, Backman, Valgerdur M, Gudmundsson, Larus, Kristjansson, Kristleifur, Bergthorsson, Jon T, Kostic, Jelena, Frigge, Michael L, Geller, Frank, Gudbjartsson, Daniel, Sigurdsson, Helgi, Jonsdottir, Thora, Hrafnkelsson, Jon, Johannsson, Jakob, Sveinsson, Thorarinn, Myrdal, Gardar, Grimsson, Hlynur Niels, Jonsson, Thorvaldur, von Holst, Susanna, Werelius, Barbro, Margolin, Sara, Lindblom, Annika, Mayordomo, Jose I, Haiman, Christopher A, Kiemeney, Lambertus A, Johannsson, Oskar Th, Gulcher, Jeffrey R, Thorsteinsdottir, Unnur, Kong, Augustine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.07.2007
• Subjects: Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Case-Control Studies; Chromosomes; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 2 - genetics; Classical genetics, quantitative genetics, hybrids; Diagnosis; Estrogen; Estrogens; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic aspects; Genetic Predisposition to Disease; Genetic Variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Gynecology. Andrology. Obstetrics; Health risks; Humans; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; Methods, theories and miscellaneous; Physiological aspects; Receptors; Receptors, Estrogen - biosynthesis; Risk factors; Single nucleotide polymorphisms; Tumors; Netherlands; Genetic mapping; Variant; Mammary gland diseases; Estrogen receptor; Chromosome; Breast cancer; Malignant tumor
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng2064

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: ∼25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5′ end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.