Fine scale mapping of the breast cancer 16q12 locus

• Published in: Human molecular genetics Vol. 19; no. 12; pp. 2507 - 2515
• Main Authors: Udler, Miriam S., Ahmed, Shahana, Healey, Catherine S., Meyer, Kerstin, Struewing, Jeffrey, Maranian, Melanie, Kwon, Erika M., Zhang, Jinghui, Tyrer, Jonathan, Karlins, Eric, Platte, Radka, Kalmyrzaev, Bolot, Dicks, Ed, Field, Helen, Maia, Ana-Teresa, Prathalingam, Radhika, Teschendorff, Andrew, McArthur, Stewart, Doody, David R., Luben, Robert, Caldas, Carlos, Bernstein, Leslie, Kolonel, Laurence K., Henderson, Brian E., Wu, Anna H., Le Marchand, Loic, Ursin, Giske, Press, Michael F., Lindblom, Annika, Margolin, Sara, Shen, Chen-Yang, Yang, Show-Lin, Hsiung, Chia-Ni, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Malone, Kathleen E., Haiman, Christopher A., Pharoah, Paul D., Ponder, Bruce A.J., Ostrander, Elaine A., Easton, Douglas F., Dunning, Alison M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.06.2010
• Subjects: Association Studies; Biological and medical sciences; Breast Neoplasms - genetics; Chromosome Mapping; Chromosomes, Human, Pair 16 - genetics; Classical genetics, quantitative genetics, hybrids; Female; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Methods, theories and miscellaneous; Molecular and cellular biology; Polymorphism, Single Nucleotide; Tumors; Genetic mapping; Mammary gland diseases; Breast disease; Genetics; Breast cancer; Malignant tumor; Locus; Cancer
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddq122

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.