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; Ovarian Cancer Association Consortium; A Gentry-Maharaj; U Menon; E Hogdall; Susanne Krüger Kjær; 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, Ovarian Cancer Association Consortium, A Gentry-Maharaj, U Menon, E Hogdall, Susanne Krüger Kjær, A Whittemore, R DiCioccio, H Song, S A GaytherS J Ramus, P D P Pharaoh, E L Goode

35 Citations (Scopus)

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) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) 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), P=0.01] 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), P=0.02]. 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
Journal	British Journal of Cancer
Volume	101
Issue number	8
Pages (from-to)	1461-8
Number of pages	7
ISSN	0007-0920
DOIs	https://doi.org/10.1038/sj.bjc.6605284
Publication status	Published - 2009

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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., Ovarian Cancer Association Consortium, Gentry-Maharaj, A., Menon, U., Hogdall, E., Kjær, S. K., Whittemore, A., DiCioccio, R., Song, H., ... Goode, E. L. (2009). Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis. British Journal of Cancer, 101(8), 1461-8. 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, Ovarian Cancer Association Consortium, Gentry-Maharaj, A, Menon, U, Hogdall, E, Kjær, SK, 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. 1461-8. https://doi.org/10.1038/sj.bjc.6605284

@article{abc54ed072c611df928f000ea68e967b,

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) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) 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), P=0.01] 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), P=0.02]. 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.",

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 {Ovarian Cancer Association Consortium} and A Gentry-Maharaj and U Menon and E Hogdall and Kj{\ae}r, {Susanne Kr{\"u}ger} 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 = "Keywords: Cell Cycle; Cyclin-Dependent Kinases; Female; Genetic Predisposition to Disease; Humans; Ovarian Neoplasms; Polymorphism, Single Nucleotide",

year = "2009",

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

language = "English",

volume = "101",

pages = "1461--8",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "nature publishing group",

number = "8",

}

TY - JOUR

T1 - Cell cycle genes and ovarian cancer susceptibility: 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 - Ovarian Cancer Association Consortium

AU - Gentry-Maharaj, A

AU - Menon, U

AU - Hogdall, E

AU - Kjær, Susanne Krüger

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 - Keywords: Cell Cycle; Cyclin-Dependent Kinases; Female; Genetic Predisposition to Disease; Humans; Ovarian Neoplasms; Polymorphism, Single Nucleotide

PY - 2009

Y1 - 2009

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) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) 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), P=0.01] 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), P=0.02]. 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) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) 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), P=0.01] 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), P=0.02]. 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.

U2 - 10.1038/sj.bjc.6605284

DO - 10.1038/sj.bjc.6605284

M3 - Journal article

C2 - 19738611

SN - 0007-0920

VL - 101

SP - 1461

EP - 1468

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis

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