Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : implications for risk prediction. / Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Neuhausen, Susan L; Ding, Yuan Chun; Rebbeck, Timothy R; Weitzel, Jeffrey N; Lynch, Henry T; Isaacs, Claudine; Ganz, Patricia A; Tomlinson, Gail; Olopade, Olufunmilayo I; Couch, Fergus J; Wang, Xianshu; Lindor, Noralane M; Pankratz, Vernon S; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Viel, Alessandra; Allavena, Anna; Dall'Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I; Zikan, Michal; Claes, Kathleen; Poppe, Bruce; Foretova, Lenka; Mai, Phuong L; Greene, Mark H; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Ozcelik, Hilmi; Andrulis, Irene L; Thomassen, Mads; Gerdes, Anne-Marie; Sunde, Lone; Cruger, Dorthe; Birk Jensen, Uffe; Caligo, Maria; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Jernström, Helena; Stenmark-Askmalm, Marie; Ontario Cancer Genetics Network.

In: Cancer Research, Vol. 70, No. 23, 01.12.2010, p. 9742-54.

Research output: Contribution to journalArticle

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Antoniou, AC, Beesley, J, McGuffog, L, Sinilnikova, OM, Healey, S, Neuhausen, SL, Ding, YC, Rebbeck, TR, Weitzel, JN, Lynch, HT, Isaacs, C, Ganz, PA, Tomlinson, G, Olopade, OI, Couch, FJ, Wang, X, Lindor, NM, Pankratz, VS, Radice, P, Manoukian, S, Peissel, B, Zaffaroni, D, Barile, M, Viel, A, Allavena, A, Dall'Olio, V, Peterlongo, P, Szabo, CI, Zikan, M, Claes, K, Poppe, B, Foretova, L, Mai, PL, Greene, MH, Rennert, G, Lejbkowicz, F, Glendon, G, Ozcelik, H, Andrulis, IL, Thomassen, M, Gerdes, A-M, Sunde, L, Cruger, D, Birk Jensen, U, Caligo, M, Friedman, E, Kaufman, B, Laitman, Y, Jernström, H, Stenmark-Askmalm, M & Ontario Cancer Genetics Network 2010, 'Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction', Cancer Research, vol. 70, no. 23, pp. 9742-54. https://doi.org/10.1158/0008-5472.CAN-10-1907, https://doi.org/10.1158/0008-5472.CAN-10-1907

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Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL, Ding YC, Rebbeck TR, Weitzel JN, Lynch HT, Isaacs C, Ganz PA, Tomlinson G, Olopade OI, Couch FJ, Wang X, Lindor NM, Pankratz VS, Radice P, Manoukian S, Peissel B, Zaffaroni D, Barile M, Viel A, Allavena A, Dall'Olio V, Peterlongo P, Szabo CI, Zikan M, Claes K, Poppe B, Foretova L, Mai PL, Greene MH, Rennert G, Lejbkowicz F, Glendon G, Ozcelik H, Andrulis IL, Thomassen M, Gerdes A-M, Sunde L, Cruger D, Birk Jensen U, Caligo M, Friedman E, Kaufman B, Laitman Y, Jernström H, Stenmark-Askmalm M, Ontario Cancer Genetics Network. 2010. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction. Cancer Research. 70(23):9742-54. https://doi.org/10.1158/0008-5472.CAN-10-1907, https://doi.org/10.1158/0008-5472.CAN-10-1907

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Antoniou, Antonis C ; Beesley, Jonathan ; McGuffog, Lesley ; Sinilnikova, Olga M ; Healey, Sue ; Neuhausen, Susan L ; Ding, Yuan Chun ; Rebbeck, Timothy R ; Weitzel, Jeffrey N ; Lynch, Henry T ; Isaacs, Claudine ; Ganz, Patricia A ; Tomlinson, Gail ; Olopade, Olufunmilayo I ; Couch, Fergus J ; Wang, Xianshu ; Lindor, Noralane M ; Pankratz, Vernon S ; Radice, Paolo ; Manoukian, Siranoush ; Peissel, Bernard ; Zaffaroni, Daniela ; Barile, Monica ; Viel, Alessandra ; Allavena, Anna ; Dall'Olio, Valentina ; Peterlongo, Paolo ; Szabo, Csilla I ; Zikan, Michal ; Claes, Kathleen ; Poppe, Bruce ; Foretova, Lenka ; Mai, Phuong L ; Greene, Mark H ; Rennert, Gad ; Lejbkowicz, Flavio ; Glendon, Gord ; Ozcelik, Hilmi ; Andrulis, Irene L ; Thomassen, Mads ; Gerdes, Anne-Marie ; Sunde, Lone ; Cruger, Dorthe ; Birk Jensen, Uffe ; Caligo, Maria ; Friedman, Eitan ; Kaufman, Bella ; Laitman, Yael ; Jernström, Helena ; Stenmark-Askmalm, Marie ; Ontario Cancer Genetics Network. / Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : implications for risk prediction. In: Cancer Research. 2010 ; Vol. 70, No. 23. pp. 9742-54.

RIS

TY - JOUR

T1 - Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers

T2 - Cancer research. Supplement

AU - Antoniou, Antonis C

AU - Beesley, Jonathan

AU - McGuffog, Lesley

AU - Sinilnikova, Olga M

AU - Healey, Sue

AU - Neuhausen, Susan L

AU - Ding, Yuan Chun

AU - Rebbeck, Timothy R

AU - Weitzel, Jeffrey N

AU - Lynch, Henry T

AU - Isaacs, Claudine

AU - Ganz, Patricia A

AU - Tomlinson, Gail

AU - Olopade, Olufunmilayo I

AU - Couch, Fergus J

AU - Wang, Xianshu

AU - Lindor, Noralane M

AU - Pankratz, Vernon S

AU - Radice, Paolo

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Zaffaroni, Daniela

AU - Barile, Monica

AU - Viel, Alessandra

AU - Allavena, Anna

AU - Dall'Olio, Valentina

AU - Peterlongo, Paolo

AU - Szabo, Csilla I

AU - Zikan, Michal

AU - Claes, Kathleen

AU - Poppe, Bruce

AU - Foretova, Lenka

AU - Mai, Phuong L

AU - Greene, Mark H

AU - Rennert, Gad

AU - Lejbkowicz, Flavio

AU - Glendon, Gord

AU - Ozcelik, Hilmi

AU - Andrulis, Irene L

AU - Thomassen, Mads

AU - Gerdes, Anne-Marie

AU - Sunde, Lone

AU - Cruger, Dorthe

AU - Birk Jensen, Uffe

AU - Caligo, Maria

AU - Friedman, Eitan

AU - Kaufman, Bella

AU - Laitman, Yael

AU - Jernström, Helena

AU - Stenmark-Askmalm, Marie

AU - Ontario Cancer Genetics Network

PY - 2010/12/1

Y1 - 2010/12/1

N2 - The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.

AB - The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - BRCA1 Protein

KW - BRCA2 Protein

KW - Breast Neoplasms

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Heterozygote

KW - Humans

KW - Middle Aged

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Receptors, Progesterone

KW - Risk Assessment

KW - Risk Factors

KW - Sodium-Bicarbonate Symporters

KW - Survival Analysis

KW - Vesicular Transport Proteins

U2 - 10.1158/0008-5472.CAN-10-1907

DO - 10.1158/0008-5472.CAN-10-1907

M3 - Article

VL - 70

SP - 9742

EP - 9754

JO - Cancer research. Supplement

JF - Cancer research. Supplement

SN - 1538-7445

IS - 23

ER -