Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Breast Cancer Family Registry

doi:10.1186/bcr3052

Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Breast Cancer Family Registry

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Worts Causeway, Cambridge, CB1 8RN, UK.

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

Abstract

INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.

METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.

RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.

CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.

Original language	English
Pages (from-to)	R110
Journal	Breast Cancer Research
Volume	13
Issue number	6
DOIs	https://doi.org/10.1186/bcr3052
Publication status	Published - 2011

Keywords

Alleles
Breast Neoplasms/classification
Female
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Heterozygote
Humans
Mutation
Polymorphism, Single Nucleotide
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Risk

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/bcr3052

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@article{57c4e4cb5846471cb38c674767a69594,

title = "Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2",

abstract = "INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.",

keywords = "Alleles, Breast Neoplasms/classification, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen/metabolism, Receptors, Progesterone/metabolism, Risk",

author = "{Breast Cancer Family Registry} and Mulligan, {Anna Marie} and Couch, {Fergus J} and Daniel Barrowdale and Domchek, {Susan M} and Diana Eccles and Heli Nevanlinna and Ramus, {Susan J} and Mark Robson and Mark Sherman and Spurdle, {Amanda B} and Barbara Wappenschmidt and Andrew Lee and Lesley McGuffog and Sue Healey and Sinilnikova, {Olga M} and Ramunas Janavicius and Hansen, {Thomas vO} and Nielsen, {Finn C} and Bent Ejlertsen and Ana Osorio and Iv{\'a}n Mu{\~n}oz-Repeto and Mercedes Dur{\'a}n and Javier Godino and Maroulio Pertesi and Javier Ben{\'i}tez and Paolo Peterlongo and Siranoush Manoukian and Bernard Peissel and Daniela Zaffaroni and Elisa Cattaneo and Bernardo Bonanni and Alessandra Viel and Barbara Pasini and Laura Papi and Laura Ottini and Antonella Savarese and Loris Bernard and Paolo Radice and Ute Hamann and Martijn Verheus and Meijers-Heijboer, {Hanne E J} and Juul Wijnen and {G{\'o}mez Garc{\'i}a}, {Encarna B} and Nelen, {Marcel R} and Kets, {C Marleen} and Caroline Seynaeve and Tilanus-Linthorst, {Madeleine M A} and {van der Luijt}, {Rob B} and Julian Barwell and Alex Murray",

year = "2011",

doi = "10.1186/bcr3052",

language = "English",

volume = "13",

pages = "R110",

journal = "Breast Cancer Research",

issn = "1465-542X",

publisher = "BioMed Central",

number = "6",

}

TY - JOUR

T1 - Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers

T2 - results from the Consortium of Investigators of Modifiers of BRCA1/2

AU - Breast Cancer Family Registry

AU - Mulligan, Anna Marie

AU - Couch, Fergus J

AU - Barrowdale, Daniel

AU - Domchek, Susan M

AU - Eccles, Diana

AU - Nevanlinna, Heli

AU - Ramus, Susan J

AU - Robson, Mark

AU - Sherman, Mark

AU - Spurdle, Amanda B

AU - Wappenschmidt, Barbara

AU - Lee, Andrew

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Sinilnikova, Olga M

AU - Janavicius, Ramunas

AU - Hansen, Thomas vO

AU - Nielsen, Finn C

AU - Ejlertsen, Bent

AU - Osorio, Ana

AU - Muñoz-Repeto, Iván

AU - Durán, Mercedes

AU - Godino, Javier

AU - Pertesi, Maroulio

AU - Benítez, Javier

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Zaffaroni, Daniela

AU - Cattaneo, Elisa

AU - Bonanni, Bernardo

AU - Viel, Alessandra

AU - Pasini, Barbara

AU - Papi, Laura

AU - Ottini, Laura

AU - Savarese, Antonella

AU - Bernard, Loris

AU - Radice, Paolo

AU - Hamann, Ute

AU - Verheus, Martijn

AU - Meijers-Heijboer, Hanne E J

AU - Wijnen, Juul

AU - Gómez García, Encarna B

AU - Nelen, Marcel R

AU - Kets, C Marleen

AU - Seynaeve, Caroline

AU - Tilanus-Linthorst, Madeleine M A

AU - van der Luijt, Rob B

AU - Barwell, Julian

AU - Murray, Alex

PY - 2011

Y1 - 2011

N2 - INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.

AB - INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.

KW - Alleles

KW - Breast Neoplasms/classification

KW - Female

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genetic Predisposition to Disease

KW - Heterozygote

KW - Humans

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen/metabolism

KW - Receptors, Progesterone/metabolism

KW - Risk

U2 - 10.1186/bcr3052

DO - 10.1186/bcr3052

M3 - Article

C2 - 22053997

SN - 1465-542X

VL - 13

SP - R110

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 6

ER -

Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract

Keywords

UN SDGs

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