A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Honglin Song; Susan J Ramus; Jonathan Tyrer; Kelly L Bolton; Aleksandra Gentry-Maharaj; Eva Wozniak; Hoda Anton-Culver; Jenny Chang-Claude; Daniel W Cramer; Richard DiCioccio; Thilo Dörk; Ellen L Goode; Marc T Goodman; Joellen M Schildkraut; Thomas Sellers; Laura Baglietto; Matthias W Beckmann; Jonathan Beesley; Jan Blaakaer; Michael E Carney; Stephen Chanock; Zhihua Chen; Julie M Cunningham; Ed Dicks; Jennifer A Doherty; Matthias Dürst; Arif B Ekici; David Fenstermacher; Brooke L Fridley; Graham Giles; Martin E Gore; Immaculata De Vivo; Peter Hillemanns; Claus Hogdall; Estrid Hogdall; Edwin S Iversen; Ian J Jacobs; Anna Jakubowska; Dong Li; Jolanta Lissowska; Jan Lubiński; Galina Lurie; Valerie McGuire; John McLaughlin; Krzysztof Medrek; Patricia G Moorman; Kirsten Moysich; Steven Narod; Catherine Phelan; Susanne Krüger Kjaer; Australian Cancer (Ovarian) Study

doi:10.1038/ng.424

A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Honglin Song, Susan J Ramus, Jonathan Tyrer, Kelly L Bolton, Aleksandra Gentry-Maharaj, Eva Wozniak, Hoda Anton-Culver, Jenny Chang-Claude, Daniel W Cramer, Richard DiCioccio, Thilo Dörk, Ellen L Goode, Marc T Goodman, Joellen M Schildkraut, Thomas Sellers, Laura Baglietto, Matthias W Beckmann, Jonathan Beesley, Jan Blaakaer, Michael E CarneyStephen Chanock, Zhihua Chen, Julie M Cunningham, Ed Dicks, Jennifer A Doherty, Matthias Dürst, Arif B Ekici, David Fenstermacher, Brooke L Fridley, Graham Giles, Martin E Gore, Immaculata De Vivo, Peter Hillemanns, Claus Hogdall, Estrid Hogdall, Edwin S Iversen, Ian J Jacobs, Anna Jakubowska, Dong Li, Jolanta Lissowska, Jan Lubiński, Galina Lurie, Valerie McGuire, John McLaughlin, Krzysztof Medrek, Patricia G Moorman, Kirsten Moysich, Steven Narod, Catherine Phelan, Susanne Krüger Kjaer, Australian Cancer (Ovarian) Study

270 Citationer (Scopus)

Abstract

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	41
Udgave nummer	9
Sider (fra-til)	996-1000
Antal sider	5
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.424
Status	Udgivet - sep. 2009
Udgivet eksternt	Ja

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10.1038/ng.424

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Song, H., Ramus, S. J., Tyrer, J., Bolton, K. L., Gentry-Maharaj, A., Wozniak, E., Anton-Culver, H., Chang-Claude, J., Cramer, D. W., DiCioccio, R., Dörk, T., Goode, E. L., Goodman, M. T., Schildkraut, J. M., Sellers, T., Baglietto, L., Beckmann, M. W., Beesley, J., Blaakaer, J., ... Australian Cancer (Ovarian) Study (2009). A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature Genetics, 41(9), 996-1000. https://doi.org/10.1038/ng.424

Song, H, Ramus, SJ, Tyrer, J, Bolton, KL, Gentry-Maharaj, A, Wozniak, E, Anton-Culver, H, Chang-Claude, J, Cramer, DW, DiCioccio, R, Dörk, T, Goode, EL, Goodman, MT, Schildkraut, JM, Sellers, T, Baglietto, L, Beckmann, MW, Beesley, J, Blaakaer, J, Carney, ME, Chanock, S, Chen, Z, Cunningham, JM, Dicks, E, Doherty, JA, Dürst, M, Ekici, AB, Fenstermacher, D, Fridley, BL, Giles, G, Gore, ME, De Vivo, I, Hillemanns, P, Hogdall, C, Hogdall, E, Iversen, ES, Jacobs, IJ, Jakubowska, A, Li, D, Lissowska, J, Lubiński, J, Lurie, G, McGuire, V, McLaughlin, J, Medrek, K, Moorman, PG, Moysich, K, Narod, S, Phelan, C, Kjaer, SK & Australian Cancer (Ovarian) Study 2009, 'A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2', Nature Genetics, bind 41, nr. 9, s. 996-1000. https://doi.org/10.1038/ng.424

@article{8d282f62247543e5930e5515c303e77a,

title = "A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2",

abstract = "Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).",

keywords = "Alleles, Australia, Base Sequence, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 9, Confidence Intervals, Europe, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Heterozygote, Homozygote, Humans, Linkage Disequilibrium, Molecular Sequence Data, Odds Ratio, Ovarian Neoplasms/genetics, Polymorphism, Single Nucleotide, Risk Factors, United States, White People/genetics",

author = "Honglin Song and Ramus, {Susan J} and Jonathan Tyrer and Bolton, {Kelly L} and Aleksandra Gentry-Maharaj and Eva Wozniak and Hoda Anton-Culver and Jenny Chang-Claude and Cramer, {Daniel W} and Richard DiCioccio and Thilo D{\"o}rk and Goode, {Ellen L} and Goodman, {Marc T} and Schildkraut, {Joellen M} and Thomas Sellers and Laura Baglietto and Beckmann, {Matthias W} and Jonathan Beesley and Jan Blaakaer and Carney, {Michael E} and Stephen Chanock and Zhihua Chen and Cunningham, {Julie M} and Ed Dicks and Doherty, {Jennifer A} and Matthias D{\"u}rst and Ekici, {Arif B} and David Fenstermacher and Fridley, {Brooke L} and Graham Giles and Gore, {Martin E} and {De Vivo}, Immaculata and Peter Hillemanns and Claus Hogdall and Estrid Hogdall and Iversen, {Edwin S} and Jacobs, {Ian J} and Anna Jakubowska and Dong Li and Jolanta Lissowska and Jan Lubi{\'n}ski and Galina Lurie and Valerie McGuire and John McLaughlin and Krzysztof Medrek and Moorman, {Patricia G} and Kirsten Moysich and Steven Narod and Catherine Phelan and Kjaer, {Susanne Kr{\"u}ger} and {Australian Cancer (Ovarian) Study}",

year = "2009",

month = sep,

doi = "10.1038/ng.424",

language = "English",

volume = "41",

pages = "996--1000",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "9",

}

TY - JOUR

T1 - A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

AU - Song, Honglin

AU - Ramus, Susan J

AU - Tyrer, Jonathan

AU - Bolton, Kelly L

AU - Gentry-Maharaj, Aleksandra

AU - Wozniak, Eva

AU - Anton-Culver, Hoda

AU - Chang-Claude, Jenny

AU - Cramer, Daniel W

AU - DiCioccio, Richard

AU - Dörk, Thilo

AU - Goode, Ellen L

AU - Goodman, Marc T

AU - Schildkraut, Joellen M

AU - Sellers, Thomas

AU - Baglietto, Laura

AU - Beckmann, Matthias W

AU - Beesley, Jonathan

AU - Blaakaer, Jan

AU - Carney, Michael E

AU - Chanock, Stephen

AU - Chen, Zhihua

AU - Cunningham, Julie M

AU - Dicks, Ed

AU - Doherty, Jennifer A

AU - Dürst, Matthias

AU - Ekici, Arif B

AU - Fenstermacher, David

AU - Fridley, Brooke L

AU - Giles, Graham

AU - Gore, Martin E

AU - De Vivo, Immaculata

AU - Hillemanns, Peter

AU - Hogdall, Claus

AU - Hogdall, Estrid

AU - Iversen, Edwin S

AU - Jacobs, Ian J

AU - Jakubowska, Anna

AU - Li, Dong

AU - Lissowska, Jolanta

AU - Lubiński, Jan

AU - Lurie, Galina

AU - McGuire, Valerie

AU - McLaughlin, John

AU - Medrek, Krzysztof

AU - Moorman, Patricia G

AU - Moysich, Kirsten

AU - Narod, Steven

AU - Phelan, Catherine

AU - Kjaer, Susanne Krüger

AU - Australian Cancer (Ovarian) Study

PY - 2009/9

Y1 - 2009/9

N2 - Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

AB - Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

KW - Alleles

KW - Australia

KW - Base Sequence

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 9

KW - Confidence Intervals

KW - Europe

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Haplotypes

KW - Heterozygote

KW - Homozygote

KW - Humans

KW - Linkage Disequilibrium

KW - Molecular Sequence Data

KW - Odds Ratio

KW - Ovarian Neoplasms/genetics

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - United States

KW - White People/genetics

U2 - 10.1038/ng.424

DO - 10.1038/ng.424

M3 - Journal article

C2 - 19648919

SN - 1061-4036

VL - 41

SP - 996

EP - 1000

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

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