ABSTRACT INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers / Antoniou AC; Kuchenbaecker KB; Soucy P; Beesley J; Chen X; McGuffog L; Lee A; Barrowdale D; Healey S; Sinilnikova OM; Caligo MA; Loman N; Harbst K; Lindblom A; Arver B; Rosenquist R; Karlsson P; Nathanson K; Domchek S; Rebbeck T; Jakubowska A; Lubinski J; Jaworska K; Durda K; Złowowcka-Perłowska E; Osorio A; Durán M; Andrés R; Benítez J; Hamann U; Hogervorst FB; van Os TA; Verhoef S; Meijers-Heijboer HE; Wijnen J; Gómez Garcia EB; Ligtenberg MJ; Kriege M; Collée JM; Ausems MG; Oosterwijk JC; Peock S; Frost D; Ellis SD; Platte R; Fineberg E; Evans DG; Lalloo F; Jacobs C; Eeles R; Adlard J; Davidson R; Cole T; Cook J; Paterson J; Douglas F; Brewer C; Hodgson S; Morrison PJ; Walker L; Rogers MT; Donaldson A; Dorkins H; Godwin AK; Bove B; Stoppa-Lyonnet D; Houdayer C; Buecher B; de Pauw A; Mazoyer S; Calender A; Léoné M; Bressac-de Paillerets B; Caron O; Sobol H; Frenay M; Prieur F; Ferrer SF; Mortemousque I; Buys S; Daly M; Miron A; Terry MB; Hopper JL; John EM; Southey M; Goldgar D; Singer CF; Fink-Retter A; Tea MK; Kaulich DG; Hansen TV; Nielsen FC; Barkardottir RB; Gaudet M; Kirchhoff T; Joseph V; Dutra-Clarke A; Offit K; Piedmonte M; Kirk J; Cohn D; Hurteau J; Byron J; Fiorica J; Toland AE; Montagna M; Oliani C; Imyanitov E; Isaacs C; Tihomirova L; Blanco I; Lazaro C; Teulé A; Valle JD; Gayther SA; Odunsi K; Gross J; Karlan BY; Olah E; Teo SH; Ganz PA; Beattie MS; Dorfling CM; van Rensburg EJ; Diez O; Kwong A; Schmutzler RK; Wappenschmidt B; Engel C; Meindl A; Ditsch N; Arnold N; Heidemann S; Niederacher D; Preisler-Adams S; Gadzicki D; Varon-Mateeva R; Deissler H; Gehrig A; Sutter C; Kast K; Fiebig B; Schäfer D; Caldes T; de la Hoya M; Nevanlinna H; Muranen TA; Lespérance B; Spurdle AB; Neuhausen SL; Ding YC; Wang X; Fredericksen Z; Pankratz VS; Lindor NM; Peterlongo P; Manoukian S; Peissel B; Zaffaroni D; Bonanni B; Bernard L; Dolcetti R; Papi L; Ottini L; Radice P; Greene MH; Loud JT; Andrulis IL; Ozcelik H; Mulligan AM; Glendon G; Thomassen M; Gerdes AM; Jensen UB; Skytte AB; Kruse TA; Chenevix-Trench G; Couch FJ; Simard J; Easton DF. - In: BREAST CANCER RESEARCH. - ISSN 1465-542X. - STAMPA. - 14:(2012), pp. 0-0. [10.1186/bcr3121]
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers.
PAPI, LAURA;
2012
Abstract
ABSTRACT INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
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