A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

Ellen L Goode; Georgia Chenevix-Trench; Honglin Song; Susan J Ramus; Maria Notaridou; Kate Lawrenson; Martin Widschwendter; Robert A Vierkant; Melissa C Larson; Susanne K Kjaer; Michael J Birrer; Andrew Berchuck; Joellen Schildkraut; Ian Tomlinson; Lambertus A Kiemeney; Linda S Cook; Jacek Gronwald; Montserrat Garcia-Closas; Martin E Gore; Ian Campbell; Alice S Whittemore; Rebecca Sutphen; Catherine Phelan; Hoda Anton-Culver; Celeste Leigh Pearce; Diether Lambrechts; Mary Anne Rossing; Jenny Chang-Claude; Kirsten B Moysich; Marc T Goodman; Thilo Dörk; Heli Nevanlinna; Roberta B Ness; Thorunn Rafnar; Claus Hogdall; Estrid Hogdall; Brooke L Fridley; Julie M Cunningham; Weiva Sieh; Valerie McGuire; Andrew K Godwin; Daniel W Cramer; Dena Hernandez; Douglas Levine; Karen Lu; Edwin S Iversen; Rachel T Palmieri; Richard Houlston; Anne M van Altena; Katja K H Aben; Wellcome Trust Case-Control Consortium

doi:http://dx.doi.org/10.1038/ng.668

A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

Ellen L Goode, Georgia Chenevix-Trench, Honglin Song, Susan J Ramus, Maria Notaridou, Kate Lawrenson, Martin Widschwendter, Robert A Vierkant, Melissa C Larson, Susanne K Kjaer, Michael J Birrer, Andrew Berchuck, Joellen Schildkraut, Ian Tomlinson, Lambertus A Kiemeney, Linda S Cook, Jacek Gronwald, Montserrat Garcia-Closas, Martin E Gore, Ian CampbellAlice S Whittemore, Rebecca Sutphen, Catherine Phelan, Hoda Anton-Culver, Celeste Leigh Pearce, Diether Lambrechts, Mary Anne Rossing, Jenny Chang-Claude, Kirsten B Moysich, Marc T Goodman, Thilo Dörk, Heli Nevanlinna, Roberta B Ness, Thorunn Rafnar, Claus Hogdall, Estrid Hogdall, Brooke L Fridley, Julie M Cunningham, Weiva Sieh, Valerie McGuire, Andrew K Godwin, Daniel W Cramer, Dena Hernandez, Douglas Levine, Karen Lu, Edwin S Iversen, Rachel T Palmieri, Richard Houlston, Anne M van Altena, Katja K H Aben, Wellcome Trust Case-Control Consortium

Faculty of Health and Medical Sciences

270 Citations (Scopus)

Abstract

Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P 10 -4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P -5 × 10 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

Original language	English
Journal	Nature Genetics
Volume	42
Issue number	10
Pages (from-to)	874-9
Number of pages	6
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.668
Publication status	Published - 1 Oct 2010

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Goode, E. L., Chenevix-Trench, G., Song, H., Ramus, S. J., Notaridou, M., Lawrenson, K., Widschwendter, M., Vierkant, R. A., Larson, M. C., Kjaer, S. K., Birrer, M. J., Berchuck, A., Schildkraut, J., Tomlinson, I., Kiemeney, L. A., Cook, L. S., Gronwald, J., Garcia-Closas, M., Gore, M. E., ... Wellcome Trust Case-Control Consortium (2010). A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature Genetics, 42(10), 874-9. https://doi.org/10.1038/ng.668

Goode, EL, Chenevix-Trench, G, Song, H, Ramus, SJ, Notaridou, M, Lawrenson, K, Widschwendter, M, Vierkant, RA, Larson, MC, Kjaer, SK, Birrer, MJ, Berchuck, A, Schildkraut, J, Tomlinson, I, Kiemeney, LA, Cook, LS, Gronwald, J, Garcia-Closas, M, Gore, ME, Campbell, I, Whittemore, AS, Sutphen, R, Phelan, C, Anton-Culver, H, Pearce, CL, Lambrechts, D, Rossing, MA, Chang-Claude, J, Moysich, KB, Goodman, MT, Dörk, T, Nevanlinna, H, Ness, RB, Rafnar, T, Hogdall, C, Hogdall, E, Fridley, BL, Cunningham, JM, Sieh, W, McGuire, V, Godwin, AK, Cramer, DW, Hernandez, D, Levine, D, Lu, K, Iversen, ES, Palmieri, RT, Houlston, R, van Altena, AM, Aben, KKH & Wellcome Trust Case-Control Consortium 2010, 'A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24', Nature Genetics, vol. 42, no. 10, pp. 874-9. https://doi.org/10.1038/ng.668

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title = "A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24",

abstract = "Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P 10 -4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P -5 × 10 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.",

author = "Goode, {Ellen L} and Georgia Chenevix-Trench and Honglin Song and Ramus, {Susan J} and Maria Notaridou and Kate Lawrenson and Martin Widschwendter and Vierkant, {Robert A} and Larson, {Melissa C} and Kjaer, {Susanne K} and Birrer, {Michael J} and Andrew Berchuck and Joellen Schildkraut and Ian Tomlinson and Kiemeney, {Lambertus A} and Cook, {Linda S} and Jacek Gronwald and Montserrat Garcia-Closas and Gore, {Martin E} and Ian Campbell and Whittemore, {Alice S} and Rebecca Sutphen and Catherine Phelan and Hoda Anton-Culver and Pearce, {Celeste Leigh} and Diether Lambrechts and Rossing, {Mary Anne} and Jenny Chang-Claude and Moysich, {Kirsten B} and Goodman, {Marc T} and Thilo D{\"o}rk and Heli Nevanlinna and Ness, {Roberta B} and Thorunn Rafnar and Claus Hogdall and Estrid Hogdall and Fridley, {Brooke L} and Cunningham, {Julie M} and Weiva Sieh and Valerie McGuire and Godwin, {Andrew K} and Cramer, {Daniel W} and Dena Hernandez and Douglas Levine and Karen Lu and Iversen, {Edwin S} and Palmieri, {Rachel T} and Richard Houlston and {van Altena}, {Anne M} and Aben, {Katja K H} and H{\o}gdall, {Claus Kim}",

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T1 - A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

AU - Goode, Ellen L

AU - Chenevix-Trench, Georgia

AU - Song, Honglin

AU - Ramus, Susan J

AU - Notaridou, Maria

AU - Lawrenson, Kate

AU - Widschwendter, Martin

AU - Vierkant, Robert A

AU - Larson, Melissa C

AU - Kjaer, Susanne K

AU - Birrer, Michael J

AU - Berchuck, Andrew

AU - Schildkraut, Joellen

AU - Tomlinson, Ian

AU - Kiemeney, Lambertus A

AU - Cook, Linda S

AU - Gronwald, Jacek

AU - Garcia-Closas, Montserrat

AU - Gore, Martin E

AU - Campbell, Ian

AU - Whittemore, Alice S

AU - Sutphen, Rebecca

AU - Phelan, Catherine

AU - Anton-Culver, Hoda

AU - Pearce, Celeste Leigh

AU - Lambrechts, Diether

AU - Rossing, Mary Anne

AU - Chang-Claude, Jenny

AU - Moysich, Kirsten B

AU - Goodman, Marc T

AU - Dörk, Thilo

AU - Nevanlinna, Heli

AU - Ness, Roberta B

AU - Rafnar, Thorunn

AU - Hogdall, Claus

AU - Hogdall, Estrid

AU - Fridley, Brooke L

AU - Cunningham, Julie M

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Godwin, Andrew K

AU - Cramer, Daniel W

AU - Hernandez, Dena

AU - Levine, Douglas

AU - Lu, Karen

AU - Iversen, Edwin S

AU - Palmieri, Rachel T

AU - Houlston, Richard

AU - van Altena, Anne M

AU - Aben, Katja K H

AU - Wellcome Trust Case-Control Consortium

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P 10 -4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P -5 × 10 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

AB - Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P 10 -4) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P -5 × 10 -8 (8q24, P = 8.0 × 10 -15 and 2q31, P = 3.8 × 10 -14) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10 -8 and 17q21, P = 1.4 × 10 -7). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

U2 - http://dx.doi.org/10.1038/ng.668

DO - http://dx.doi.org/10.1038/ng.668

M3 - Journal article

SN - 1061-4036

VL - 42

SP - 874

EP - 879

JO - Nature: New biology

JF - Nature: New biology

IS - 10

ER -

A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24

Abstract

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