Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis

J. M. Cunningham; R. A. Vierkant; T. A. Sellers; C. Phelan; D. N. Rider; M. Liebow; J. Schildkraut; A. Berchuck; F. J. Couch; X. Wang; B. L. Fridley; A. Gentry-Maharaj; U. Menon; E. Hogdall; S. Kjaer; A. Whittemore; R. Dicioccio; H. Song; S. A. Gayther; S. J. Ramus; P. D.P. Pharaoh; E. L. Goode

doi:10.1038/sj.bjc.6605284

Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis

J. M. Cunningham, R. A. Vierkant, T. A. Sellers, C. Phelan, D. N. Rider, M. Liebow, J. Schildkraut, A. Berchuck, F. J. Couch, X. Wang, B. L. Fridley, A. Gentry-Maharaj, U. Menon, E. Hogdall, S. Kjaer, A. Whittemore, R. Dicioccio, H. Song, S. A. Gayther, S. J. RamusP. D.P. Pharaoh, E. L. Goode

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

35 Scopus citations

Abstract

Background:Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods:We examined single nucleotide polymorphisms (SNPs) (n288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n829) and ovarian cancer-free controls (n941) were genotyped using an Illumina assay.Results:Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population odds ratio, OR BB vs AA 2.81 (1.29-6.09), P0.01 was also observed in a replication population, and the association remained suggestive in the combined analysis OR BB vs AA 1.59 (1.08-2.34), P0.02. No other SNP associations remained suggestive in the replication populations.Conclusion:ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

Original language	English (US)
Pages (from-to)	1461-1468
Number of pages	8
Journal	British journal of cancer
Volume	101
Issue number	8
DOIs	https://doi.org/10.1038/sj.bjc.6605284
State	Published - Oct 20 2009

Keywords

Cell cycle
Ovarian cancer
Tag SNPs genes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/sj.bjc.6605284

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Cunningham, J. M., Vierkant, R. A., Sellers, T. A., Phelan, C., Rider, D. N., Liebow, M., Schildkraut, J., Berchuck, A., Couch, F. J., Wang, X., Fridley, B. L., Gentry-Maharaj, A., Menon, U., Hogdall, E., Kjaer, S., Whittemore, A., Dicioccio, R., Song, H., Gayther, S. A., ... Goode, E. L. (2009). Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis. British journal of cancer, 101(8), 1461-1468. https://doi.org/10.1038/sj.bjc.6605284

Cunningham, JM, Vierkant, RA, Sellers, TA, Phelan, C, Rider, DN, Liebow, M, Schildkraut, J, Berchuck, A, Couch, FJ, Wang, X, Fridley, BL, Gentry-Maharaj, A, Menon, U, Hogdall, E, Kjaer, S, Whittemore, A, Dicioccio, R, Song, H, Gayther, SA, Ramus, SJ, Pharaoh, PDP & Goode, EL 2009, 'Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis', British journal of cancer, vol. 101, no. 8, pp. 1461-1468. https://doi.org/10.1038/sj.bjc.6605284

@article{4eacc446f6ab45a5853aec072c3b975a,

title = "Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis",

abstract = "Background:Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods:We examined single nucleotide polymorphisms (SNPs) (n288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n829) and ovarian cancer-free controls (n941) were genotyped using an Illumina assay.Results:Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population odds ratio, OR BB vs AA 2.81 (1.29-6.09), P0.01 was also observed in a replication population, and the association remained suggestive in the combined analysis OR BB vs AA 1.59 (1.08-2.34), P0.02. No other SNP associations remained suggestive in the replication populations.Conclusion:ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.",

keywords = "Cell cycle, Ovarian cancer, Tag SNPs genes",

author = "Cunningham, {J. M.} and Vierkant, {R. A.} and Sellers, {T. A.} and C. Phelan and Rider, {D. N.} and M. Liebow and J. Schildkraut and A. Berchuck and Couch, {F. J.} and X. Wang and Fridley, {B. L.} and A. Gentry-Maharaj and U. Menon and E. Hogdall and S. Kjaer and A. Whittemore and R. Dicioccio and H. Song and Gayther, {S. A.} and Ramus, {S. J.} and Pharaoh, {P. D.P.} and Goode, {E. L.}",

note = "Funding Information: Profound thanks are expressed for the study participants contributing to the project. We are also grateful to the family and friends of Kathryn Sladek Smith for their generous support of the Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. This work was supported in part by NIH grants CA 122443 and CA 88868, as well as grant CA15083, which supports the Mayo Clinic College of Medicine Genotyping Shared Resource. Grant support: National Cancer Institute, grants R01 CA88868, R01 CA122443 and CA15083.",

year = "2009",

month = oct,

day = "20",

doi = "10.1038/sj.bjc.6605284",

language = "English (US)",

volume = "101",

pages = "1461--1468",

journal = "British journal of cancer",

issn = "0007-0920",

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number = "8",

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TY - JOUR

T1 - Cell cycle genes and ovarian cancer susceptibility

T2 - A tagSNP analysis

AU - Cunningham, J. M.

AU - Vierkant, R. A.

AU - Sellers, T. A.

AU - Phelan, C.

AU - Rider, D. N.

AU - Liebow, M.

AU - Schildkraut, J.

AU - Berchuck, A.

AU - Couch, F. J.

AU - Wang, X.

AU - Fridley, B. L.

AU - Gentry-Maharaj, A.

AU - Menon, U.

AU - Hogdall, E.

AU - Kjaer, S.

AU - Whittemore, A.

AU - Dicioccio, R.

AU - Song, H.

AU - Gayther, S. A.

AU - Ramus, S. J.

AU - Pharaoh, P. D.P.

AU - Goode, E. L.

N1 - Funding Information: Profound thanks are expressed for the study participants contributing to the project. We are also grateful to the family and friends of Kathryn Sladek Smith for their generous support of the Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. This work was supported in part by NIH grants CA 122443 and CA 88868, as well as grant CA15083, which supports the Mayo Clinic College of Medicine Genotyping Shared Resource. Grant support: National Cancer Institute, grants R01 CA88868, R01 CA122443 and CA15083.

PY - 2009/10/20

Y1 - 2009/10/20

N2 - Background:Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods:We examined single nucleotide polymorphisms (SNPs) (n288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n829) and ovarian cancer-free controls (n941) were genotyped using an Illumina assay.Results:Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population odds ratio, OR BB vs AA 2.81 (1.29-6.09), P0.01 was also observed in a replication population, and the association remained suggestive in the combined analysis OR BB vs AA 1.59 (1.08-2.34), P0.02. No other SNP associations remained suggestive in the replication populations.Conclusion:ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

AB - Background:Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods:We examined single nucleotide polymorphisms (SNPs) (n288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n829) and ovarian cancer-free controls (n941) were genotyped using an Illumina assay.Results:Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population odds ratio, OR BB vs AA 2.81 (1.29-6.09), P0.01 was also observed in a replication population, and the association remained suggestive in the combined analysis OR BB vs AA 1.59 (1.08-2.34), P0.02. No other SNP associations remained suggestive in the replication populations.Conclusion:ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

KW - Cell cycle

KW - Ovarian cancer

KW - Tag SNPs genes

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Cell cycle genes and ovarian cancer susceptibility: A tagSNP analysis

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