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Title: Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers.
Authors: Antoniou AC,  Sinilnikova OM,  McGuffog L,  Healey S,  Nevanlinna H,  Heikkinen T,  Simard J,  Spurdle AB,  Beesley J,  Chen X,  Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer,  Neuhausen SL,  Ding YC,  Couch FJ,  Wang X,  Fredericksen Z,  Peterlongo P,  Peissel B,  Bonanni B,  Viel A,  Bernard L,  Radice P,  Szabo CI,  Foretova L,  Zikan M,  Claes K,  Greene MH,  Mai PL,  Rennert G,  Lejbkowicz F,  Andrulis IL,  Ozcelik H,  Glendon G,  OCGN,  Gerdes AM,  Thomassen M,  Sunde L,  Caligo MA,  Laitman Y,  Kontorovich T,  Cohen S,  Kaufman B,  Dagan E,  Baruch RG,  Friedman E,  Harbst K,  Barbany-Bustinza G,  Rantala J,  Ehrencrona H,  Karlsson P,  Domchek SM,  Nathanson KL,  Osorio A,  Blanco I,  Lasa A,  Benítez J,  Hamann U,  Hogervorst FB,  Rookus MA,  Collee JM,  Devilee P,  Ligtenberg MJ,  van der Luijt RB,  Aalfs CM,  Waisfisz Q,  Wijnen J,  van Roozendaal CE,  HEBON,  Peock S,  Cook M,  Frost D,  Oliver C,  Platte R,  Evans DG,  Lalloo F,  Eeles R,  Izatt L,  Davidson R,  Chu C,  Eccles D,  Cole T,  Hodgson S,  EMBRACE,  Godwin AK,  Stoppa-Lyonnet D,  Buecher B,  Léoné M,  Bressac-de Paillerets B,  Remenieras A,  Caron O,  Lenoir GM,  Sevenet N,  Longy M,  Ferrer SF,  Prieur F,  GEMO,  Goldgar D,  Miron A,  John EM,  Buys SS,  Daly MB,  Hopper JL,  Terry MB,  Yassin Y,  Breast Cancer Family Registry,  Singer C,  Gschwantler-Kaulich D,  Staudigl C,  Hansen Tv,  Barkardottir RB,  Kirchhoff T,  Pal P,  Kosarin K,  Offit K,  Piedmonte M,  Rodriguez GC,  Wakeley K,  Boggess JF,  Basil J,  Schwartz PE,  Blank SV,  Toland AE,  Montagna M,  Casella C,  Imyanitov EN,  Allavena A,  Schmutzler RK,  Versmold B,  Engel C,  Meindl A,  Ditsch N,  Arnold N,  Niederacher D,  Deissler H,  Fiebig B,  Suttner C,  Schönbuchner I,  Gadzicki D,  Caldes T,  de la Hoya M,  Pooley KA,  Easton DF,  Chenevix-Trench G,  CIMBA
Journal: Hum Mol Genet
Date: 2009 Nov 15
Branches: CGB
PubMed ID: 19656774
PMC ID: PMC2782243
Abstract: Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.