Fine scale mapping of the breast cancer 16q12 locus.
Human Molecular Genetics 2010 ; 19: 2507-15.
Udler MS, Ahmed S, Healey CS, Meyer K, Struewing J, Maranian M, Kwon EM, Zhang J, Tyrer J, Karlins E, Platte R, Kalmyrzaev B, Dicks E, Field H, Maia AT, Prathalingam R, Teschendorff A, McArthur S, Doody DR, Luben R, Caldas C, Bernstein L, Kolonel LK, Henderson BE, Wu AH, Le Marchand L, Ursin G, Press MF, Lindblom A, Margolin S, Shen CY, Yang SL, Hsiung CN, Kang D, Yoo KY, Noh DY, Ahn SH, Malone KE, Haiman CA, Pharoah PD, Ponder BA, Ostrander EA, Easton DF, Dunning AM
DOI : 10.1093/hmg/ddq122
PubMed ID : 20332101
PMCID : PMC2876886
Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5' end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case-control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case-control studies exhibit a different pattern of association suggestive of an additional causative variant.