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. 2007 Sep 19;8 Suppl 1(Suppl 1):S6.
doi: 10.1186/1471-2350-8-S1-S6.

A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

Joanne M Murabito  1 , Carol L Rosenberg, Daniel Finger, Bernard E Kreger, Daniel Levy, Greta Lee Splansky, Karen Antman, Shih-Jen Hwang
Affiliations

A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

Joanne M Murabito et al. BMC Med Genet. .

Abstract

Background: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified.

Methods: We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits--prostate cancer and breast cancer--in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate > or =80%, minor allele frequency > or =10%, Hardy-Weinberg test p > or = 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT).

Results: There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 x 10(-8) in COL1A1; and prostate cancer, rs9311171, p = 1.75 x 10(-6) in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

Conclusion: Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility.

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References

    1. American Cancer Society. Cancer Facts and Figures 2006. Atlanta: American Cancer Society; 2006.
    1. 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, Luccarini C, Conroy D, Shah M, Munday H, Jordan C, Perkins B, West J, Redman K, 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 OA, 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, Aghmesheh M, Amor D, Andrews L, Antill Y, Armes J, Armitage S, Arnold L, Balleine R, Begley G, Beilby J, Bennett I, Bennett B, Berry G, Blackburn A, Brennan M, Brown M, Buckley M, Burke J, Butow P, Byron K, Callen D, Campbell I, Chenevix-Trench G, Clarke C, Colley A, Cotton D, Cui J, Culling B, Cummings M, Dawson SJ, Dixon J, Dobrovic A, Dudding T, Edkins T, Eisenbruch M, Farshid G, Fawcett S, Field M, Firgaira F, Fleming J, Forbes J, Friedlander M, Gaff C, Gardner M, Gattas M, George P, Giles G, Gill G, Goldblatt J, Greening S, Grist S, Haan E, Harris M, Hart S, Hayward N, Hopper J, Humphrey E, Jenkins M, Jones A, Kefford R, Kirk J, Kollias J, Kovalenko S, Lakhani S, Leary J, Lim J, Lindeman G, Lipton L, Lobb L, Maclurcan M, Mann G, Marsh D, McCredie M, McKay M, Anne MS, Meiser B, Milne R, Mitchell G, Newman B, O'loughlin I, Osborne R, Peters L, Phillips K, Price M, Reeve J, Reeve T, Richards R, Rinehart G, Robinson B, Rudzki B, Salisbury E, Sambrook J, Saunders C, Scott C, Scott E, Scott R, Seshadri R, Shelling A, Southey M, Spurdle A, Suthers G, Taylor D, Tennant C, Thorne H, Townshend S, Tucker K, Tyler J, Venter D, Visvader J, Walpole I, Ward R, Waring P, Warner B, Warren G, Watson E, Williams R, Wilson J, Winship I, Young MA, Bowtell D, Green A, Defazio A, Chenevix-Trench G, Gertig D, Webb P, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BA. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007. in press . - PMC - PubMed
    1. 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. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007. in press . - PMC - PubMed
    1. Cupples LA, Arruda H, Benjamin EJ, D'Agostino RB Sr, Demissie S, DeStefano AL, Dupuis J, Falls K, Fox CS, Gottlieb D, Govindaraju DR, Guo CY, Heard-Costa N, Hwang SJ, Katherisan S, Kiel D, Laramie JM, Larson MG, Levy D, Liu CY, Lunetta KL, Mailman M, Manning AK, Meigs JB, Murabito JM, Newton-Cheh C, O'Connor GT, O'Donnell CJ, Pandey MA, Seshadri S, Vasan RS, Wang ZY, Wilk JB, Wolf PA, Yang Q, Atwood LD. The Framingham Heart Study 100K SNP genome-wide association study resource: Overview of 17 phenotype working group reports. BMC Med Genet. 2007;8(Suppl 1):S1. - PMC - PubMed
    1. Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006;38:652–658. doi: 10.1038/ng1808. - DOI - PubMed

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