Human Genetics

, Volume 132, Issue 5, pp 523–536 | Cite as

Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation

  • Erica S. Rinella
  • Yongzhao Shao
  • Lauren Yackowski
  • Sreemanta Pramanik
  • Ruth Oratz
  • Freya Schnabel
  • Saurav Guha
  • Charles LeDuc
  • Christopher L. Campbell
  • Susan D. Klugman
  • Mary Beth Terry
  • Ruby T. Senie
  • Irene L. Andrulis
  • Mary Daly
  • Esther M. John
  • Daniel Roses
  • Wendy K. Chung
  • Harry Ostrer
Original Investigation

Abstract

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.

Notes

Acknowledgments

The authors gratefully acknowledge the generous contribution of the patients who participated in this study. We also wish to thank Gord Glendon, Teresa Selander, Nayana Weerasooriya and members and participants in the Ontario Familial Breast Cancer Registry for their contributions to the study. We would like to thank Dr. Susan Love Army of Women, Peter Pressman from Weill Cornell Medical College, and Ina Ratner of Maimonides Medical Center for their help with recruitment. Finally we would like to thank Dr. Bert Gold from the National Cancer Institute–Frederick for his help with obtaining data for the MSKCC dataset.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics statement

This study was performed under the NYU School of Medicine Institutional Review Board-approved protocol, “Genetic Modifiers of Breast and Ovarian Cancer Risk” (07-333).

References

  1. Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dork T, Schurmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomaki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M et al (2009) Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41:585–590. doi: 10.1038/ng.354 PubMedCrossRefGoogle Scholar
  2. Ahn MJ, Won HH, Lee J, Lee ST, Sun JM, Park YH, Ahn JS, Kwon OJ, Kim H, Shim YM, Kim J, Kim K, Kim YH, Park JY, Kim JW, Park K (2012) The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations. Hum Genet 131:365–372. doi: 10.1007/s00439-011-1080-z PubMedCrossRefGoogle Scholar
  3. Cazier JB, Tomlinson I (2010) General lessons from large-scale studies to identify human cancer predisposition genes. J Pathol 220:255–262. doi: 10.1002/path.2650 PubMedCrossRefGoogle Scholar
  4. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MW, Pooley KA, Scollen S, Baynes C, Ponder BA, Chanock S, Lissowska J, Brinton L, Peplonska B, Southey MC, Hopper JL, McCredie MR, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojesen SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claude J, Kropp S, Risch A, Wang-Gohrke S, Schurmann P, Bogdanova N, Dork T, Fagerholm R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, Renwick A, Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G, Beesley J, Mannermaa A, Hartikainen J, Kataja V, Kosma VM, Couch FJ, Olson JE, Goode EL, Broeks A, Schmidt MK, Hogervorst FB, Van’t Veer LJ, Kang D, Yoo KY, Noh DY, Ahn SH, Wedren S, Hall P, Low YL, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdson AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PD, Easton DF (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 39:352–358. doi: 10.1038/ng1981 PubMedCrossRefGoogle Scholar
  5. Dyrso T, Li J, Wang K, Lindebjerg J, Kolvraa S, Bolund L, Jakobsen A, Bruun-Petersen G, Li S, Cruger DG (2011) Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization. Cancer Genet 204:84–95. doi: 10.1016/j.cancergencyto.2010.08.019 PubMedCrossRefGoogle Scholar
  6. Easton DF (1999) How many more breast cancer predisposition genes are there? Breast Cancer Res 1:14–17PubMedCrossRefGoogle Scholar
  7. Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schurmann P, Dork T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093. doi: 10.1038/nature05887 PubMedCrossRefGoogle Scholar
  8. Fallin MD, Lasseter VK, Wolyniec PS, McGrath JA, Nestadt G, Valle D, Liang KY, Pulver AE (2004) Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families. Am J Hum Genet 75:204–219. doi: 10.1086/422474 PubMedCrossRefGoogle Scholar
  9. Fletcher O, Johnson N, Orr N, Hosking FJ, Gibson LJ, Walker K, Zelenika D, Gut I, Heath S, Palles C, Coupland B, Broderick P, Schoemaker M, Jones M, Williamson J, Chilcott-Burns S, Tomczyk K, Simpson G, Jacobs KB, Chanock SJ, Hunter DJ, Tomlinson IP, Swerdlow A, Ashworth A, Ross G, dos Santos Silva I, Lathrop M, Houlston RS, Peto J (2011) Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 103:425–435. doi: 10.1093/jnci/djq563 PubMedCrossRefGoogle Scholar
  10. Gail MH (2008) Discriminatory accuracy from single-nucleotide polymorphisms in models to predict breast cancer risk. J Natl Cancer Inst 100:1037–1041Google Scholar
  11. Gold B, Kirchhoff T, Stefanov S, Lautenberger J, Viale A, Garber J, Friedman E, Narod S, Olshen AB, Gregersen P, Kosarin K, Olsh A, Bergeron J, Ellis NA, Klein RJ, Clark AG, Norton L, Dean M, Boyd J, Offit K (2008) Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci USA 105:4340–4345. doi: 10.1073/pnas.0800441105 PubMedCrossRefGoogle Scholar
  12. Gravel S, Henn BM, Gutenkunst RN, Indap AR, Marth GT, Clark AG, Yu F, Gibbs RA, Bustamante CD (2011) Demographic history and rare allele sharing among human populations. Proc Natl Acad Sci USA 108:11983–11988. doi: 10.1073/pnas.1019276108 PubMedCrossRefGoogle Scholar
  13. Guthery SL, Salisbury BA, Pungliya MS, Stephens JC, Bamshad M (2007) The structure of common genetic variation in United States populations. Am J Hum Genet 81:1221–1231. doi: 10.1086/522239 PubMedCrossRefGoogle Scholar
  14. Haiman CA, Stram DO (2010) Exploring genetic susceptibility to cancer in diverse populations. Curr Opin Genet Dev 20:330–335. doi: 10.1016/j.gde.2010.02.007 PubMedCrossRefGoogle Scholar
  15. Hameed M, Ulger C, Yasar D, Limaye N, Kurvathi R, Streck D, Benevenia J, Patterson F, Dermody JJ, Toruner GA (2009) Genome profiling of chondrosarcoma using oligonucleotide array-based comparative genomic hybridization. Cancer Genet Cytogenet 192:56–59. doi: 10.1016/j.cancergencyto.2009.03.009 PubMedCrossRefGoogle Scholar
  16. Harlid S, Ivarsson MI, Butt S, Grzybowska E, Eyfjord JE, Lenner P, Forsti A, Hemminki K, Manjer J, Dillner J, Carlson J (2012) Combined effect of low-penetrant SNPs on breast cancer risk. Br J Cancer 106:389–396. doi: 10.1038/bjc.2011.461 PubMedCrossRefGoogle Scholar
  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. doi: 10.1136/bmj.327.7414.557 PubMedCrossRefGoogle Scholar
  18. Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Thomas G, Chanock SJ (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39:870–874. doi: 10.1038/ng2075 PubMedCrossRefGoogle Scholar
  19. Janer M, Friedrichsen DM, Stanford JL, Badzioch MD, Kolb S, Deutsch K, Peters MA, Goode EL, Welti R, DeFrance HB, Iwasaki L, Li S, Hood L, Ostrander EA, Jarvik GP (2003) Genomic scan of 254 hereditary prostate cancer families. Prostate 57:309–319. doi: 10.1002/pros.10305 PubMedCrossRefGoogle Scholar
  20. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300. doi: 10.3322/caac.20073 PubMedCrossRefGoogle Scholar
  21. John EM, Hopper JL, Beck JC, Knight JA, Neuhausen SL, Senie RT, Ziogas A, Andrulis IL, Anton-Culver H, Boyd N, Buys SS, Daly MB, O’Malley FP, Santella RM, Southey MC, Venne VL, Venter DJ, West DW, Whittemore AS, Seminara D (2004) The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer. Breast Cancer Res 6:R375–R389. doi: 10.1186/bcr801 PubMedCrossRefGoogle Scholar
  22. Kenny EE PeI, Karban A, Ozelius L, Mitchell AA, Ng SM, Erazo M, Ostrer H, Abraham C, Abreu MT, Atzmon G, Barzilai N, Brant S, Burns ER, Chowers Y, Clark LN, Darvasi A, Doheny D, Duerr RH, Eliakim R, Giladi N, Gregersen PK, Hakonarson H, Jones MR, McGovern DPB, Mulle J, Orr-Urtreger A, Proctor DD, Pulver A, Rotter JI, Silverberg MS, Ullman T, Warren ST, Waterman M, Zhang W, Bergman A, Mayer L, Katz S, Desnick RJ, Cho JH, Peter I (2012) A genome-wide scan of Ashkenazi Jewish Crohn’s disease suggests novel susceptibility loci. PLoS Genet 8:e1002559Google Scholar
  23. Kim SW, Kim JW, Kim YT, Kim JH, Kim S, Yoon BS, Nam EJ, Kim HY (2007) Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: potential predictive markers of chemoresistant disease. Genes Chromosomes Cancer 46:1–9. doi: 10.1002/gcc.20384 PubMedCrossRefGoogle Scholar
  24. Kuukasjarvi T, Karhu R, Tanner M, Kahkonen M, Schaffer A, Nupponen N, Pennanen S, Kallioniemi A, Kallioniemi OP, Isola J (1997) Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res 57:1597–1604PubMedGoogle Scholar
  25. Li J, Humphreys K, Heikkinen T, Aittomaki K, Blomqvist C, Pharoah PD, Dunning AM, Ahmed S, Hooning MJ, Martens JW, van den Ouweland AM, Alfredsson L, Palotie A, Peltonen-Palotie L, Irwanto A, Low HQ, Teoh GH, Thalamuthu A, Easton DF, Nevanlinna H, Liu J, Czene K, Hall P (2011) A combined analysis of genome-wide association studies in breast cancer. Breast Cancer Res Treat 126:717–727. doi: 10.1007/s10549-010-1172-9 PubMedCrossRefGoogle Scholar
  26. Liu X, Cheng R, Verbitsky M, Kisselev S, Browne A, Mejia-Sanatana H, Louis ED, Cote LJ, Andrews H, Waters C, Ford B, Frucht S, Fahn S, Marder K, Clark LN, Lee JH (2011) Genome-wide association study identifies candidate genes for Parkinson’s disease in an Ashkenazi Jewish population. BMC Med Genet 12:104. doi: 10.1186/1471-2350-12-104 PubMedCrossRefGoogle Scholar
  27. Long J, Cai Q, Shu XO, Qu S, Li C, Zheng Y, Gu K, Wang W, Xiang YB, Cheng J, Chen K, Zhang L, Zheng H, Shen CY, Huang CS, Hou MF, Shen H, Hu Z, Wang F, Deming SL, Kelley MC, Shrubsole MJ, Khoo US, Chan KY, Chan SY, Haiman CA, Henderson BE, Le Marchand L, Iwasaki M, Kasuga Y, Tsugane S, Matsuo K, Tajima K, Iwata H, Huang B, Shi J, Li G, Wen W, Gao YT, Lu W, Zheng W (2010) Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. PLoS Genet 6:e1001002. doi: 10.1371/journal.pgen.1001002 PubMedCrossRefGoogle Scholar
  28. McClellan J, King MC (2010) Genetic heterogeneity in human disease. Cell 141:210–217. doi: 10.1016/j.cell.2010.03.032 PubMedCrossRefGoogle Scholar
  29. Mitchell MK, Gregersen PK, Johnson S, Parsons R, Vlahov D (2004) The New York Cancer Project: rationale, organization, design, and baseline characteristics. J Urban Health 81:301–310PubMedCrossRefGoogle Scholar
  30. Need AC, Kasperaviciute D, Cirulli ET, Goldstein DB (2009) A genome-wide genetic signature of Jewish ancestry perfectly separates individuals with and without full Jewish ancestry in a large random sample of European Americans. Genome Biol 10:R7. doi: 10.1186/gb-2009-10-1-r7 PubMedCrossRefGoogle Scholar
  31. Negrini M, Sabbioni S, Possati L, Rattan S, Corallini A, Barbanti-Brodano G, Croce CM (1994) Suppression of tumorigenicity of breast cancer cells by microcell-mediated chromosome transfer: studies on chromosomes 6 and 11. Cancer Res 54:1331–1336PubMedGoogle Scholar
  32. Nordgard SH, Johansen FE, Alnaes GI, Bucher E, Syvanen AC, Naume B, Borresen-Dale AL, Kristensen VN (2008) Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. Genes Chromosomes Cancer 47:680–696. doi: 10.1002/gcc.20569 PubMedCrossRefGoogle Scholar
  33. Ntzani EE, Liberopoulos G, Manolio TA, Ioannidis JP (2011) Consistency of genome-wide associations across major ancestral groups. Hum Genet. doi: 10.1007/s00439-011-1124-4 PubMedGoogle Scholar
  34. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575. doi: 10.1086/519795 PubMedCrossRefGoogle Scholar
  35. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39:165–167. doi: 10.1038/ng1959 PubMedCrossRefGoogle Scholar
  36. Raskin L, Pinchev M, Arad C, Lejbkowicz F, Tamir A, Rennert HS, Rennert G, Gruber SB (2008) FGFR2 is a breast cancer susceptibility gene in Jewish and Arab Israeli populations. Cancer Epidemiol Biomarkers Prev 17:1060–1065. doi: 10.1158/1055-9965.EPI-08-0018 PubMedCrossRefGoogle Scholar
  37. Rubinstein WS (2004) Hereditary breast cancer in Jews. Fam Cancer 3:249–257. doi: 10.1007/s10689-004-9550-2 PubMedCrossRefGoogle Scholar
  38. Shifman S, Levit A, Chen ML, Chen CH, Bronstein M, Weizman A, Yakir B, Navon R, Darvasi A (2006) A complete genetic association scan of the 22q11 deletion region and functional evidence reveal an association between DGCR2 and schizophrenia. Hum Genet 120:160–170. doi: 10.1007/s00439-006-0195-0 PubMedCrossRefGoogle Scholar
  39. Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236. doi: 10.3322/caac.20121 PubMedCrossRefGoogle Scholar
  40. Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ, Albers-Akkers MT, Swinkels DW, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Godino J, Garcia-Prats MD, Polo E, Tres A, Mouy M, Saemundsdottir J, Backman VM, Gudmundsson L, Kristjansson K, Bergthorsson JT, Kostic J, Frigge ML, Geller F, Gudbjartsson D, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Jonsson T, von Holst S, Werelius B, Margolin S, Lindblom A, Mayordomo JI, Haiman CA, Kiemeney LA, Johannsson OT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39:865–869. doi: 10.1038/ng2064 PubMedCrossRefGoogle Scholar
  41. Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, Cox DG, Hankinson SE, Hutchinson A, Wang Z, Yu K, Chatterjee N, Garcia-Closas M, Gonzalez-Bosquet J, Prokunina-Olsson L, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver R, Prentice R, Jackson R, Kooperberg C, Chlebowski R, Lissowska J, Peplonska B, Brinton LA, Sigurdson A, Doody M, Bhatti P, Alexander BH, Buring J, Lee IM, Vatten LJ, Hveem K, Kumle M, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Chanock SJ, Hunter DJ (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 41:579–584. doi: 10.1038/ng.353 PubMedCrossRefGoogle Scholar
  42. Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, Seal S, Ghoussaini M, Hines S, Healey CS, Hughes D, Warren-Perry M, Tapper W, Eccles D, Evans DG, Hooning M, Schutte M, van den Ouweland A, Houlston R, Ross G, Langford C, Pharoah PD, Stratton MR, Dunning AM, Rahman N, Easton DF (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42:504–507. doi: 10.1038/ng.586 PubMedCrossRefGoogle Scholar
  43. Veltman JA, Fridlyand J, Pejavar S, Olshen AB, Korkola JE, DeVries S, Carroll P, Kuo WL, Pinkel D, Albertson D, Cordon-Cardo C, Jain AN, Waldman FM (2003) Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors. Cancer Res 63:2872–2880PubMedGoogle Scholar
  44. Wacholder S, Hartge P, Prentice R, Garcia-Closas M, Feigelson HS, Diver WR, Thun MJ, Cox DG, Hankinson SE, Kraft P, Rosner B, Berg CD, Brinton LA, Lissowska J, Sherman ME, Chlebowski R, Kooperberg C, Jackson RD, Buckman DW, Hui P, Pfeiffer R, Jacobs KB, Thomas GD, Hoover RN, Gail MH, Chanock SJ, Hunter DJ (2010) Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362:986–993Google Scholar
  45. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S, Foretova L, Soucek P, King MC (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388. doi: 10.1001/jama.295.12.1379 PubMedCrossRefGoogle Scholar
  46. Walsh T, Lee MK, Casadei S, Thornton AM, Stray SM, Pennil C, Nord AS, Mandell JB, Swisher EM, King MC (2010) Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci USA 107:12629–12633. doi: 10.1073/pnas.1007983107 PubMedCrossRefGoogle Scholar
  47. Wang K, Dickson SP, Stolle CA, Krantz ID, Goldstein DB, Hakonarson H (2010) Interpretation of association signals and identification of causal variants from genome-wide association studies. Am J Hum Genet 86:730–742. doi: 10.1016/j.ajhg.2010.04.003 PubMedCrossRefGoogle Scholar
  48. Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO (2009) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41:324–328. doi: 10.1038/ng.318 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Erica S. Rinella
    • 1
  • Yongzhao Shao
    • 2
  • Lauren Yackowski
    • 3
  • Sreemanta Pramanik
    • 4
  • Ruth Oratz
    • 12
  • Freya Schnabel
    • 1
  • Saurav Guha
    • 5
  • Charles LeDuc
    • 5
  • Christopher L. Campbell
    • 3
  • Susan D. Klugman
    • 6
  • Mary Beth Terry
    • 7
  • Ruby T. Senie
    • 7
  • Irene L. Andrulis
    • 8
  • Mary Daly
    • 9
  • Esther M. John
    • 10
    • 11
  • Daniel Roses
    • 1
  • Wendy K. Chung
    • 5
  • Harry Ostrer
    • 3
  1. 1.Department of SurgeryNew York University Langone Medical CenterNew YorkUSA
  2. 2.Division of BiostatisticsNew York University School of MedicineNew YorkUSA
  3. 3.Department of PathologyAlbert Einstein College of MedicineBronxUSA
  4. 4.Kolkata Zonal LaboratoryNational Environmental Engineering Research InstituteKolkataIndia
  5. 5.Department of PediatricsColumbia University Medical CenterNew YorkUSA
  6. 6.Department of Obstetrics and Gynecology and Women’s HealthMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA
  7. 7.Department of EpidemiologyMailman School of Public Health of Columbia UniversityNew YorkUSA
  8. 8.Department of Molecular GeneticsUniversity of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai HospitalTorontoCanada
  9. 9.Clinical GeneticsFox Chase Cancer CenterPhiladelphiaUSA
  10. 10.Cancer Prevention Institute of CaliforniaFremontUSA
  11. 11.Stanford University School of Medicine and Stanford Cancer InstituteStanfordUSA
  12. 12.Department of MedicineNew York University Langone Medical CenterNew YorkUSA

Personalised recommendations