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    PloS one. 2015 Apr 1. doi: 10.1371/journal.pone.0120020. pii: PONE-D-14-28419. pmc: PMC4382299
    Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
    Blanco I1,  Kuchenbaecker K2,  Cuadras D3,  Wang X4,  Barrowdale D5,  de Garibay GR6,  Librado P7,  Sánchez-Gracia A8,  Rozas J9,  Bonifaci N10,  McGuffog L11,  Pankratz VS12,  Islam A13,  Mateo F14,  Berenguer A15,  Petit A16,  Català I17,  Brunet J18,  Feliubadaló L19,  Tornero E20,  Benítez J21,  Osorio A22,  Ramón y Cajal T23,  Nevanlinna H24,  Aittomäki K25,  Arun BK26,  Toland AE27,  Karlan BY28,  Walsh C29,  Lester J30,  Greene MH31,  Mai PL32,  Nussbaum RL33,  Andrulis IL34,  Domchek SM35,  Nathanson KL36,  Rebbeck TR37,  Barkardottir RB38,  Jakubowska A39,  Lubinski J40,  Durda K41,  Jaworska-Bieniek K42,  Claes K43,  Van Maerken T44,  Díez O45,  Hansen TV46,  Jønson L47,  Gerdes AM48,  Ejlertsen B49,  de la Hoya M50,  Caldés T51,  Dunning AM52,  Oliver C53,  Fineberg E54,  Cook M55,  Peock S56,  McCann E57,  Murray A58,  Jacobs C59,  Pichert G60,  Lalloo F61,  Chu C62,  Dorkins H63,  Paterson J64,  Ong KR65,  Teixeira MR66,  Hogervorst FB67,  van der Hout AH68,  Seynaeve C69,  van der Luijt RB70,  Ligtenberg MJ71,  Devilee P72,  Wijnen JT73,  Rookus MA74,  Meijers-Heijboer HE75,  Blok MJ76,  van den Ouweland AM77,  Aalfs CM78,  Rodriguez GC79,  Phillips KA80,  Piedmonte M81,  Nerenstone SR82,  Bae-Jump VL83,  O'Malley DM84,  Ratner ES85,  Schmutzler RK86,  Wappenschmidt B87,  Rhiem K88,  Engel C89,  Meindl A90,  Ditsch N91,  Arnold N92,  Plendl HJ93,  Niederacher D94,  Sutter C95,  Wang-Gohrke S96,  Steinemann D97,  Preisler-Adams S98,  Kast K99,  Varon-Mateeva R100,  Gehrig A101,  Bojesen A102,  Pedersen IS103,  Sunde L104,  Jensen UB105,  Thomassen M106,  Kruse TA107,  Foretova L108,  Peterlongo P109,  Bernard L110,  Peissel B111,  Scuvera G112,  Manoukian S113,  Radice P114,  Ottini L115,  Montagna M116,  Agata S117,  Maugard C118,  Simard J119,  Soucy P120,  Berger A121,  Fink-Retter A122,  Singer CF123,  Rappaport C124,  Geschwantler-Kaulich D125,  Tea MK126,  Pfeiler G127,  John EM128,  Miron A129,  Neuhausen SL130,  Terry MB131,  Chung WK132,  Daly MB133,  Goldgar DE134,  Janavicius R135,  Dorfling CM136,  van Rensburg EJ137,  Fostira F138,  Konstantopoulou I139,  Garber J140,  Godwin AK141,  Olah E142,  Narod SA143,  Rennert G144,  Paluch SS145,  Laitman Y146,  Friedman E147,  Liljegren A148,  Rantala J149,  Stenmark-Askmalm M150,  Loman N151,  Imyanitov EN152,  Hamann U153,  Spurdle AB154,  Healey S155,  Weitzel JN156,  Herzog J157,  Margileth D158,  Gorrini C159,  Esteller M160,  Gómez A161,  Sayols S162,  Vidal E163,  Heyn H164,  Stoppa-Lyonnet D165,  Léoné M166,  Barjhoux L167,  Fassy-Colcombet M168,  de Pauw A169,  Lasset C170,  Ferrer SF171,  Castera L172,  Berthet P173,  Cornelis F174,  Bignon YJ175,  Damiola F176,  Mazoyer S177,  Sinilnikova OM178,  Maxwell CA179,  Vijai J180,  Robson M181,  Kauff N182,  Corines MJ183,  Villano D184,  Cunningham J185,  Lee A186,  Lindor N187,  Lázaro C188,  Easton DF189,  Offit K190,  Chenevix-Trench G191,  Couch FJ192,  Antoniou AC193,  Pujana MA194
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    Author information
    Abstract

    While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.


    Publikations ID: 25830658
    Quelle: öffnen
     
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