Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

被引：0

作者：

C L Pearce

A M Near

D J Van Den Berg

S J Ramus

A Gentry-Maharaj

U Menon

S A Gayther

A R Anderson

C K Edlund

A H Wu

X Chen

J Beesley

P M Webb

S K Holt

C Chen

J A Doherty

M A Rossing

A S Whittemore

V McGuire

R A DiCioccio

M T Goodman

G Lurie

M E Carney

L R Wilkens

R B Ness

K B Moysich

R Edwards

E Jennison

S K Kjaer

E Hogdall

C K Hogdall

E L Goode

T A Sellers

R A Vierkant

J C Cunningham

J M Schildkraut

A Berchuck

P G Moorman

E S Iversen

D W Cramer

K L Terry

A F Vitonis

L Titus-Ernstoff

H Song

P D P Pharoah

A B Spurdle

H Anton-Culver

A Ziogas

W Brewster

V Galitovskiy

机构：

[1] Keck School of Medicine,Department of Preventive Medicine

[2] University of Southern California,Department of Epidemiology

[3] University of Michigan School of Public Health,Division of Public Health Sciences

[4] Keck School of Medicine,Department of Health Research and Policy, Division of Epidemiology

[5] University of Southern California,Department of Cancer Genetics

[6] Gynaecological Cancer Research Laboratories,Department of Cancer Prevention and Control

[7] UCL EGA Institute for Women's Health,Department of OB/GYN/RS

[8] University College London,Department of Virus

[9] UCL EGA Institute for Women's Health,Division of Gynecologic Oncology

[10] Gynaecological Cancer Research Centre,Department of Statistical Sciences

[11] The Queensland Institute of Medical Research,Department of Community and Family Medicine and of Pediatrics

[12] Post Office Royal Brisbane Hospital,Department of Oncology

[13] Herston,Department of Epidemiology

[14] Brisbane,Department of OB/GYN

[15] QLD 4029,undefined

[16] Australia,undefined

[17] Epidemiology Program,undefined

[18] Fred Hutchinson Cancer Research Center,undefined

[19] Stanford University School of Medicine,undefined

[20] Roswell Park Cancer Institute,undefined

[21] Cancer Research Center,undefined

[22] University of Hawaii,undefined

[23] The University of Texas School of Public Health,undefined

[24] Roswell Park Cancer Institute,undefined

[25] Magee-Women's Hospital,undefined

[26] University of Pittsburgh Medical Center,undefined

[27] Gynecologic Oncologists of Northeast Ohio,undefined

[28] Hormones and Cancer,undefined

[29] Institute of Cancer Epidemiology,undefined

[30] Danish Cancer Society,undefined

[31] 2100 Copenhagen,undefined

[32] Denmark,undefined

[33] Gynaecologic Clinic,undefined

[34] Juliane Marie Centre,undefined

[35] Rigshospitalet,undefined

[36] University of Copenhagen,undefined

[37] 2100 Copenhagen,undefined

[38] Denmark,undefined

[39] Mayo Clinic College of Medicine,undefined

[40] H. Lee Moffitt Cancer Center and Research Institute,undefined

[41] MRC CANCONT,undefined

[42] Tampa,undefined

[43] FL,undefined

[44] 33612,undefined

[45] USA,undefined

[46] Cancer Prevention and Control Research Program,undefined

[47] Duke University Medical Center,undefined

[48] Duke University Medical Center,undefined

[49] Duke University,undefined

[50] Brigham and Women's Hospital,undefined

来源：

British Journal of Cancer | 2009年 / 100卷

关键词：

ovarian cancer; genetic susceptibility; oestrogen metabolism; CYP3A4; pooled-analyses;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P⩽0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: ORhomozygous(hom)=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20–6.56, P=0.017, phet across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

引用

页码：412 / 420

页数：8

共 50 条

[1] Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium
Pearce, C. L.
Near, A. M.
Van Den Berg, D. J.
Ramus, S. J.
Gentry-Maharaj, A.
Menon, U.
Gayther, S. A.
Anderson, A. R.
Edlund, C. K.
Wu, A. H.
Chen, X.
Beesley, J.
Webb, P. M.
Holt, S. K.
Chen, C.
Doherty, J. A.
Rossing, M. A.
Whittemore, A. S.
McGuire, V.
DiCioccio, R. A.
Goodman, M. T.
Lurie, G.
Carney, M. E.
Wilkens, L. R.
Ness, R. B.
Moysich, K. B.
Edwards, R.
Jennison, E.
Kjaer, S. K.
Hogdall, E.
Hogdall, C. K.
Goode, E. L.
Sellers, T. A.
Vierkant, R. A.
Cunningham, J. C.
Schildkraut, J. M.
Berchuck, A.
Moorman, P. G.
Iversen, E. S.
Cramer, D. W.
Terry, K. L.
Vitonis, A. F.
Titus-Ernstoff, L.
Song, H.
Pharoah, P. D. P.
Spurdle, A. B.
Anton-Culver, H.
Ziogas, A.
Brewster, W.
Galitovskiy, V.
BRITISH JOURNAL OF CANCER, 2009, 100 (02) : 412 - 420
[2] Erratum: Validating genetic risk associations for ovarian cancer through the International Ovarian Cancer Association Consortium
C L Pearce
A M Near
D J Van Den Berg
S J Ramus
A Gentry-Maharaj
U Menon
S A Gayther
A R Anderson
C K Edlund
A H Wu
X Chen
J Beesley
P M Webb
S K Holt
C Chen
J A Doherty
M A Rossing
A S Whittemore
V McGuire
R A DiCioccio
M T Goodman
G Lurie
M E Carney
L R Wilkens
R B Ness
K B Moysich
R Edwards
E Jennison
S K Kjaer
E Hogdall
C K Hogdall
E L Goode
T A Sellers
R A Vierkant
J M Cunningham
J M Schildkraut
A Berchuck
P G Moorman
E S Iversen
D W Cramer
K L Terry
A F Vitonis
L Titus-Ernstoff
H Song
P D P Pharoah
A B Spurdle
H Anton-Culver
A Ziogas
W Brewster
V Galitovskiy
British Journal of Cancer, 2009, 101 : 1805 - 1805
[3] Validating genetic risk associations for ovarian cancer through the International Ovarian Cancer Association Consortium (vol 100, pg 412, 2009)
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Near, A. M.
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Ramus, S. J.
Gentry-Maharaj, A.
Menon, U.
Gayther, S. A.
Anderson, A. R.
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Wu, A. H.
Chen, X.
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Webb, P. M.
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Doherty, J. A.
Rossing, M. A.
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DiCioccio, R. A.
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Iversen, E. S.
Cramer, D. W.
Terry, K. L.
Vitonis, A. F.
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Pharoah, P. D. P.
Spurdle, A. B.
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