Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

Honglin Song; Susan J. Ramus; Susanne Krüger Kjaer; Richard A. DiCioccio; Georgia Chenevix-Trench; Celeste Leigh Pearce; Estrid Hogdall; Alice S. Whittemore; Valerie McGuire; Claus Hogdall; Jan Blaakaer; Anna H. Wu; David J. Van Den Berg; Daniel O. Stram; Usha Menon; Aleksandra Gentry-Maharaj; Ian J. Jacobs; Penny M. Webb; Jonathan Beesley; Xiaoqing Chen; Mary Anne Rossing; Jennifer A. Doherty; Jenny Chang-Claude; Shan Wang-Gohrke; Marc T. Goodman; Galina Lurie; Pamela J. Thompson; Michael E. Carney; Roberta B. Ness; Kirsten Moysich; Ellen L. Goode; Robert A. Vierkant; Julie M. Cunningham; Stephanie Anderson; Joellen M. Schildkraut; Andrew Berchuck; Edwin S. Iversen; Patricia G. Moorman; Montserrat Garcia-Closas; Stephen Chanock; Jolanta Lissowska; Louise Brinton; Hoda Anton-Culver; Argyrios Ziogas; Wendy R. Brewster; Bruce A.J. Ponder; Douglas F. Easton; Simon A. Gayther; Paul D.P. Pharoah

doi:10.1093/hmg/ddp138

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

Honglin Song, Susan J. Ramus, Susanne Krüger Kjaer, Richard A. DiCioccio, Georgia Chenevix-Trench, Celeste Leigh Pearce, Estrid Hogdall, Alice S. Whittemore, Valerie McGuire, Claus Hogdall, Jan Blaakaer, Anna H. Wu, David J. Van Den Berg, Daniel O. Stram, Usha Menon, Aleksandra Gentry-Maharaj, Ian J. Jacobs, Penny M. Webb, Jonathan Beesley, Xiaoqing ChenMary Anne Rossing, Jennifer A. Doherty, Jenny Chang-Claude, Shan Wang-Gohrke, Marc T. Goodman, Galina Lurie, Pamela J. Thompson, Michael E. Carney, Roberta B. Ness, Kirsten Moysich, Ellen L. Goode, Robert A. Vierkant, Julie M. Cunningham, Stephanie Anderson, Joellen M. Schildkraut, Andrew Berchuck, Edwin S. Iversen, Patricia G. Moorman, Montserrat Garcia-Closas, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Hoda Anton-Culver, Argyrios Ziogas, Wendy R. Brewster, Bruce A.J. Ponder, Douglas F. Easton, Simon A. Gayther, Paul D.P. Pharoah

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

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Abstract

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

Original language	English (US)
Pages (from-to)	2297-2304
Number of pages	8
Journal	Human molecular genetics
Volume	18
Issue number	12
DOIs	https://doi.org/10.1093/hmg/ddp138
State	Published - 2009

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1093/hmg/ddp138

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Song, H., Ramus, S. J., Kjaer, S. K., DiCioccio, R. A., Chenevix-Trench, G., Pearce, C. L., Hogdall, E., Whittemore, A. S., McGuire, V., Hogdall, C., Blaakaer, J., Wu, A. H., Van Den Berg, D. J., Stram, D. O., Menon, U., Gentry-Maharaj, A., Jacobs, I. J., Webb, P. M., Beesley, J., ... Pharoah, P. D. P. (2009). Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study. Human molecular genetics, 18(12), 2297-2304. https://doi.org/10.1093/hmg/ddp138

Song, H, Ramus, SJ, Kjaer, SK, DiCioccio, RA, Chenevix-Trench, G, Pearce, CL, Hogdall, E, Whittemore, AS, McGuire, V, Hogdall, C, Blaakaer, J, Wu, AH, Van Den Berg, DJ, Stram, DO, Menon, U, Gentry-Maharaj, A, Jacobs, IJ, Webb, PM, Beesley, J, Chen, X, Rossing, MA, Doherty, JA, Chang-Claude, J, Wang-Gohrke, S, Goodman, MT, Lurie, G, Thompson, PJ, Carney, ME, Ness, RB, Moysich, K, Goode, EL, Vierkant, RA, Cunningham, JM, Anderson, S, Schildkraut, JM, Berchuck, A, Iversen, ES, Moorman, PG, Garcia-Closas, M, Chanock, S, Lissowska, J, Brinton, L, Anton-Culver, H, Ziogas, A, Brewster, WR, Ponder, BAJ, Easton, DF, Gayther, SA & Pharoah, PDP 2009, 'Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study', Human molecular genetics, vol. 18, no. 12, pp. 2297-2304. https://doi.org/10.1093/hmg/ddp138

@article{747ecbf426454dc5aa1cc2c5c2091144,

title = "Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study",

abstract = "Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.",

author = "Honglin Song and Ramus, {Susan J.} and Kjaer, {Susanne Kr{\"u}ger} and DiCioccio, {Richard A.} and Georgia Chenevix-Trench and Pearce, {Celeste Leigh} and Estrid Hogdall and Whittemore, {Alice S.} and Valerie McGuire and Claus Hogdall and Jan Blaakaer and Wu, {Anna H.} and {Van Den Berg}, {David J.} and Stram, {Daniel O.} and Usha Menon and Aleksandra Gentry-Maharaj and Jacobs, {Ian J.} and Webb, {Penny M.} and Jonathan Beesley and Xiaoqing Chen and Rossing, {Mary Anne} and Doherty, {Jennifer A.} and Jenny Chang-Claude and Shan Wang-Gohrke and Goodman, {Marc T.} and Galina Lurie and Thompson, {Pamela J.} and Carney, {Michael E.} and Ness, {Roberta B.} and Kirsten Moysich and Goode, {Ellen L.} and Vierkant, {Robert A.} and Cunningham, {Julie M.} and Stephanie Anderson and Schildkraut, {Joellen M.} and Andrew Berchuck and Iversen, {Edwin S.} and Moorman, {Patricia G.} and Montserrat Garcia-Closas and Stephen Chanock and Jolanta Lissowska and Louise Brinton and Hoda Anton-Culver and Argyrios Ziogas and Brewster, {Wendy R.} and Ponder, {Bruce A.J.} and Easton, {Douglas F.} and Gayther, {Simon A.} and Pharoah, {Paul D.P.}",

note = "Funding Information: We thank all the individuals who took part in this study. We thank: Hannah Munday, Barbara Perkins, Mitul Shah, Clare Jordan, Judy West, Anabel Simpson, Sue Irvine, Anne Stafford, the SEARCH team: the local general practices and nurses and the Eastern Cancer Registry for recruitment of the UK cases and the EPIC-Norfolk investigators for recruitment of the UK controls for SEA study; We thank all members of the research team, including research nurses, research scientists, data entry personnel and consultant gynae- cological oncologists for their help in establishing the UKOPS case–control collection, particularly we thank Eva Wozniak for the efforts in genotyping and Andy Ryan and Jeremy Ford for data and sample management for UKO study. We thank Ursula Eilber and Tanja Koehler for competent technical assistance for German Ovarian Cancer study. The AOCS Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www.aocstudy.org/). The AOCS and ACS Management Group (A. Green, P. Parsons, N. Hayward, P. Webb, D. Whiteman) thank all of the project staff, collaborating institutions and study participants. We thank all the funding agencies and institutions for their support. D.F.E. is a Principal Research Fellow of Cancer Research UK, P.D.P.P. is CRUK Senior Clinical Research Fellow. S.J.R. is supported by the Mermaid/Eve Appeal, G.C.T. and P.W. are supported by the NHMRC. Funding Information: This work was supported by Cancer Research UK, The Roswell Park Alliance, The Danish Cancer Society and The National Cancer Institute (CA71766, CA16056, RO1 CA61107 and RO1 CA122443). We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of OCAC through their donations to the Ovarian Cancer Research Fund. US Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study), The National Health and Medical Research Council of Australia (199600) (ACS study). DOV study was supported by the US national Cancer Institute grants R01 CA87538 and R01 CA112523. The German Ovarian Cancer Study was supported by the German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research grant 01 GB 9401 and the genotyping in part by the state of Baden-W{\"u}rttemberg through Medical Faculty of the University of Ulm (P.685). HAW study was supported by US Public Health Service grant R01-CA-58598, and contracts N01-CN-55424 and N01-PC-35137 from the National Cancer Institute, NIH, Department of Health and Human Services. UCI study was supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The UKOPS study is funded by the OAK Foundation. Some of this work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health{\textquoteright}s NIHR Biomedical Research Centre funding scheme.",

year = "2009",

doi = "10.1093/hmg/ddp138",

language = "English (US)",

volume = "18",

pages = "2297--2304",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "12",

}

TY - JOUR

T1 - Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

AU - Song, Honglin

AU - Ramus, Susan J.

AU - Kjaer, Susanne Krüger

AU - DiCioccio, Richard A.

AU - Chenevix-Trench, Georgia

AU - Pearce, Celeste Leigh

AU - Hogdall, Estrid

AU - Whittemore, Alice S.

AU - McGuire, Valerie

AU - Hogdall, Claus

AU - Blaakaer, Jan

AU - Wu, Anna H.

AU - Van Den Berg, David J.

AU - Stram, Daniel O.

AU - Menon, Usha

AU - Gentry-Maharaj, Aleksandra

AU - Jacobs, Ian J.

AU - Webb, Penny M.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Rossing, Mary Anne

AU - Doherty, Jennifer A.

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Goodman, Marc T.

AU - Lurie, Galina

AU - Thompson, Pamela J.

AU - Carney, Michael E.

AU - Ness, Roberta B.

AU - Moysich, Kirsten

AU - Goode, Ellen L.

AU - Vierkant, Robert A.

AU - Cunningham, Julie M.

AU - Anderson, Stephanie

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Iversen, Edwin S.

AU - Moorman, Patricia G.

AU - Garcia-Closas, Montserrat

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Brewster, Wendy R.

AU - Ponder, Bruce A.J.

AU - Easton, Douglas F.

AU - Gayther, Simon A.

AU - Pharoah, Paul D.P.

N1 - Funding Information: We thank all the individuals who took part in this study. We thank: Hannah Munday, Barbara Perkins, Mitul Shah, Clare Jordan, Judy West, Anabel Simpson, Sue Irvine, Anne Stafford, the SEARCH team: the local general practices and nurses and the Eastern Cancer Registry for recruitment of the UK cases and the EPIC-Norfolk investigators for recruitment of the UK controls for SEA study; We thank all members of the research team, including research nurses, research scientists, data entry personnel and consultant gynae- cological oncologists for their help in establishing the UKOPS case–control collection, particularly we thank Eva Wozniak for the efforts in genotyping and Andy Ryan and Jeremy Ford for data and sample management for UKO study. We thank Ursula Eilber and Tanja Koehler for competent technical assistance for German Ovarian Cancer study. The AOCS Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www.aocstudy.org/). The AOCS and ACS Management Group (A. Green, P. Parsons, N. Hayward, P. Webb, D. Whiteman) thank all of the project staff, collaborating institutions and study participants. We thank all the funding agencies and institutions for their support. D.F.E. is a Principal Research Fellow of Cancer Research UK, P.D.P.P. is CRUK Senior Clinical Research Fellow. S.J.R. is supported by the Mermaid/Eve Appeal, G.C.T. and P.W. are supported by the NHMRC. Funding Information: This work was supported by Cancer Research UK, The Roswell Park Alliance, The Danish Cancer Society and The National Cancer Institute (CA71766, CA16056, RO1 CA61107 and RO1 CA122443). We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of OCAC through their donations to the Ovarian Cancer Research Fund. US Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study), The National Health and Medical Research Council of Australia (199600) (ACS study). DOV study was supported by the US national Cancer Institute grants R01 CA87538 and R01 CA112523. The German Ovarian Cancer Study was supported by the German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research grant 01 GB 9401 and the genotyping in part by the state of Baden-Württemberg through Medical Faculty of the University of Ulm (P.685). HAW study was supported by US Public Health Service grant R01-CA-58598, and contracts N01-CN-55424 and N01-PC-35137 from the National Cancer Institute, NIH, Department of Health and Human Services. UCI study was supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The UKOPS study is funded by the OAK Foundation. Some of this work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centre funding scheme.

PY - 2009

Y1 - 2009

N2 - Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

AB - Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

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U2 - 10.1093/hmg/ddp138

DO - 10.1093/hmg/ddp138

M3 - Article

C2 - 19304784

AN - SCOPUS:66149156222

SN - 0964-6906

VL - 18

SP - 2297

EP - 2304

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 12

ER -

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

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