title: Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.
abstract: 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: approximately 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.
authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. simon.stacey@decode.is
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authors.forename: Thorvaldur
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authors.lastname: Mayordomo
authors.forename: Christopher A
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authors.lastname: Haiman
authors.forename: Lambertus A
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authors.lastname: Kiemeney
authors.forename: Oskar Th
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authors.lastname: Johannsson
authors.forename: Jeffrey R
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authors.lastname: Gulcher
authors.forename: Unnur
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mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D011960:Receptors, Estrogen / Q000096:biosynthesis*
chemical_list: D011960:Receptors, Estrogen