MS Udler, S Ahmed, CS Healey, K Meyer, J Struewing, M Maranian, EM Kwon, J Zhang, J Tyrer, E Karlins, R Platte, B Kalmyrzaev, E Dicks, H Field, A-T Maia, R Prathalingam, A Teschendorff, S McArthur, DR Doody, R Luben, C Caldas, L Bernstein, LK Kolonel, BE Henderson, AH Wu, L Le Marchand, G Ursin, MF Press, A Lindblom, S Margolin, C-Y Shen, S-L Yang, C-N Hsiung, D Kang, K-Y Yoo, D-Y Noh, S-H Ahn, KE Malone, CA Haiman, PD Pharoah, BAJ Ponder, EA Ostrander, DF Easton, AM Dunning
Hum Mol Genet
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.