Finding Needles in a Haystack DOI: 10.1038/Nrg2150 Less Than 25% of the Genes That That Are Known to Be Important in 2Q35 and One on 16Q12

RESEARCH HIGHLIGHTS

CANCER GENETICS Finding needles in a haystack DOI: 10.1038/nrg2150 Less than 25% of the genes that that are known to be important in 2q35 and one on 16q12. These account for the familial risk of breast prostate cancer. two alleles were also specifically URLs cancer have been identified, and David Hunter and colleagues ana- associated with the risk of oestrogen- genetic variants contributing more lysed the genotypes of 528,173 SNPs receptor-positive breast cancer. No FGFR2 http://www.ncbi.nlm.nih.gov/ moderate risk probably explain much in 1,145 cases of invasive breast can- genes in the region containing the sites/entrez?Db=gene&Cmd= of the remaining 75%. A recent pub- cer in Caucasian women and 1,142 2q35 SNP are known. The SNP on ShowDetailView&TermToSearc ′ h=2263 lication in Nature and two in Nature controls from the Nurses’ Health 16q12 is near the 5 end of TNRC9, Genetics have identified several new Study. The two most significant SNPs one of the genes identified by Easton TNRC9 breast cancer susceptibility loci using were, as in the study by Easton and and colleagues. http://www.ncbi.nlm.nih.gov/ sites/entrez?Db=gene&Cmd= genome-wide association studies. colleagues, in intron 2 of FGFR2. This These studies have furthered ShowDetailView&TermToSearc Douglas Easton and colleagues result was verified in an additional our understanding of the genetics h=27324 began with a panel of 266,722 SNPs, 1,776 cases and 2,072 controls from of breast cancer risk, and additional MAP3K1 and identified the 12,711 that were three other prospective cohorts. Both susceptibility alleles might also be http://www.ncbi.nlm.nih.gov/ most significantly different between studies indicate that there is a breast identified using this type of approach. sites/entrez?Db=gene&Cmd= Sarah Seton-Rogers, Associate Editor, ShowDetailView&TermToSearc 390 cases of familial breast cancer cancer susceptibility locus in FGFR2, h=4214 and 364 controls from the United but further work is needed to identify Nature Reviews Cancer Kingdom. These SNPs were exam- the causal variant. LSP1 ORIGINAL RESEARCH PAPERS Easton, D. F. http://www.ncbi.nlm.nih.gov/ ined in an additional 3,990 cases Simon Stacey, Kari Stefansson et al. Genome-wide association study identifies sites/entrez?Db=gene&Cmd= and 3,916 controls, and the 30 most and colleagues examined 311,524 novel breast cancer susceptibility loci. Nature ShowDetailView&TermToSearc significant SNPs were genotyped SNPs in 1,600 Icelandic patients with 27 May 2007 (doi: 10.1038/nature05887) | h=4046 in 21,860 cases of invasive breast breast cancer and 11,563 controls, Hunter, D. J. et al. A genome-wide association study identifies alleles in FGFR2 associated with risk cancer, 988 cases of carcinoma in situ and the ten SNPs with the lowest of sporadic postmenopausal breast cancer. and 22,578 controls from 22 studies. P values were genotyped in up to five Nature Genet. 27 May 2007 (doi: 10.1038/ng2075) | Six of these SNPs had a significance additional sample sets from Iceland, Stacey, S. N. et al. Common variants on chromosomes 2q35 and 16q12 confer –5 of ≤10 , and five fell within genes Sweden, Spain, The Netherlands and susceptibility to estrogen receptor-positive breast or linkage disequilibrium (LD) the United States. In all five sets, two cancer. Nature Genet. 27 May 2007 (doi: 10.1038/ ng2064) blocks containing genes. One was SNPs conferred increased risk of WEB SITE http://cgems.cancer.gov within an intron of fibroblast growth breast cancer: one on chromosome factor receptor 2 (FGFR2), which encodes a receptor tyrosine kinase that is amplified and overexpressed in breast cancer. Two fell in an LD block containing the 5′ end of trinucleotide repeat containing 9 (TNRC9), which encodes a member of the high-mobility group family of chromatin proteins. A fourth lay within another LD block containing mitogen-activated protein kinase kinase kinase 1 (MAP3K1), and the fifth SNP was in an intron of lymphocyte-specific protein 1 (LSP1), which encodes an F-actin binding and cytoskeleton-associated protein. The sixth SNP was in a region on chromosome 8 with no known genes, but was close to other loci Image courtesy of Sarah Seton-Rogers