Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

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Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. / Horne, Hisani N; Chung, Charles C; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; kConFab/AOCS Investigators; Wu, Anna H; Ven den Berg, David.

In: P L o S One, Vol. 11, No. 8, e0160316, 2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Horne, HN, Chung, CC, Zhang, H, Yu, K, Prokunina-Olsson, L, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Hopper, JL, Southey, MC, Schmidt, MK, Broeks, A, Muir, K, Lophatananon, A, Fasching, PA, Beckmann, MW, Fletcher, O, Johnson, N, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Marme, F, Guénel, P, Truong, T, Bojesen, SE, Flyger, H, Benitez, J, González-Neira, A, Anton-Culver, H, Neuhausen, SL, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Hamann, U, Nevanlinna, H, Khan, S, Matsuo, K, Iwata, H, Dörk, T, Bogdanova, NV, Lindblom, A, Margolin, S, Mannermaa, A, Kosma, V-M, Chenevix-Trench, G, kConFab/AOCS Investigators, Wu, AH & Ven den Berg, D 2016, 'Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus', P L o S One, vol. 11, no. 8, e0160316. https://doi.org/10.1371/journal.pone.0160316

APA

Horne, H. N., Chung, C. C., Zhang, H., Yu, K., Prokunina-Olsson, L., Michailidou, K., ... Ven den Berg, D. (2016). Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. P L o S One, 11(8), [e0160316]. https://doi.org/10.1371/journal.pone.0160316

Vancouver

Horne HN, Chung CC, Zhang H, Yu K, Prokunina-Olsson L, Michailidou K et al. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. P L o S One. 2016;11(8). e0160316. https://doi.org/10.1371/journal.pone.0160316

Author

Horne, Hisani N ; Chung, Charles C ; Zhang, Han ; Yu, Kai ; Prokunina-Olsson, Ludmila ; Michailidou, Kyriaki ; Bolla, Manjeet K ; Wang, Qin ; Dennis, Joe ; Hopper, John L ; Southey, Melissa C ; Schmidt, Marjanka K ; Broeks, Annegien ; Muir, Kenneth ; Lophatananon, Artitaya ; Fasching, Peter A ; Beckmann, Matthias W ; Fletcher, Olivia ; Johnson, Nichola ; Sawyer, Elinor J ; Tomlinson, Ian ; Burwinkel, Barbara ; Marme, Frederik ; Guénel, Pascal ; Truong, Thérèse ; Bojesen, Stig E ; Flyger, Henrik ; Benitez, Javier ; González-Neira, Anna ; Anton-Culver, Hoda ; Neuhausen, Susan L ; Brenner, Hermann ; Arndt, Volker ; Meindl, Alfons ; Schmutzler, Rita K ; Brauch, Hiltrud ; Hamann, Ute ; Nevanlinna, Heli ; Khan, Sofia ; Matsuo, Keitaro ; Iwata, Hiroji ; Dörk, Thilo ; Bogdanova, Natalia V ; Lindblom, Annika ; Margolin, Sara ; Mannermaa, Arto ; Kosma, Veli-Matti ; Chenevix-Trench, Georgia ; kConFab/AOCS Investigators ; Wu, Anna H ; Ven den Berg, David. / Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. In: P L o S One. 2016 ; Vol. 11, No. 8.

Bibtex

@article{2b0016ca206e46f19cb04d6bdd8cfafb,
title = "Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus",
abstract = "The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95{\%} confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.",
keywords = "Journal Article",
author = "Horne, {Hisani N} and Chung, {Charles C} and Han Zhang and Kai Yu and Ludmila Prokunina-Olsson and Kyriaki Michailidou and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Hopper, {John L} and Southey, {Melissa C} and Schmidt, {Marjanka K} and Annegien Broeks and Kenneth Muir and Artitaya Lophatananon and Fasching, {Peter A} and Beckmann, {Matthias W} and Olivia Fletcher and Nichola Johnson and Sawyer, {Elinor J} and Ian Tomlinson and Barbara Burwinkel and Frederik Marme and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Bojesen, {Stig E} and Henrik Flyger and Javier Benitez and Anna Gonz{\'a}lez-Neira and Hoda Anton-Culver and Neuhausen, {Susan L} and Hermann Brenner and Volker Arndt and Alfons Meindl and Schmutzler, {Rita K} and Hiltrud Brauch and Ute Hamann and Heli Nevanlinna and Sofia Khan and Keitaro Matsuo and Hiroji Iwata and Thilo D{\"o}rk and Bogdanova, {Natalia V} and Annika Lindblom and Sara Margolin and Arto Mannermaa and Veli-Matti Kosma and Georgia Chenevix-Trench and {kConFab/AOCS Investigators} and Wu, {Anna H} and {Ven den Berg}, David",
year = "2016",
doi = "10.1371/journal.pone.0160316",
language = "English",
volume = "11",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

AU - Horne, Hisani N

AU - Chung, Charles C

AU - Zhang, Han

AU - Yu, Kai

AU - Prokunina-Olsson, Ludmila

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Hopper, John L

AU - Southey, Melissa C

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Fasching, Peter A

AU - Beckmann, Matthias W

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Sawyer, Elinor J

AU - Tomlinson, Ian

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Bojesen, Stig E

AU - Flyger, Henrik

AU - Benitez, Javier

AU - González-Neira, Anna

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Nevanlinna, Heli

AU - Khan, Sofia

AU - Matsuo, Keitaro

AU - Iwata, Hiroji

AU - Dörk, Thilo

AU - Bogdanova, Natalia V

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kosma, Veli-Matti

AU - Chenevix-Trench, Georgia

AU - kConFab/AOCS Investigators

AU - Wu, Anna H

AU - Ven den Berg, David

PY - 2016

Y1 - 2016

N2 - The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

AB - The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

KW - Journal Article

U2 - 10.1371/journal.pone.0160316

DO - 10.1371/journal.pone.0160316

M3 - Journal article

C2 - 27556229

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 8

M1 - e0160316

ER -

ID: 167555936