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

被引：51

作者：

Pearce, C. L. ^{[1
]}

Near, A. M. ^{[2
]}

Van Den Berg, D. J.

Ramus, S. J. ^{[3
]}

Gentry-Maharaj, A. ^{[4
]}

Menon, U. ^{[4
]}

Gayther, S. A. ^{[3
]}

Anderson, A. R. ^{[1
]}

Edlund, C. K.

Wu, A. H. ^{[1
]}

Chen, X. ^{[5
]}

Beesley, J. ^{[5
]}

Webb, P. M. ^{[5
]}

Holt, S. K. ^{[6
]}

Chen, C. ^{[6
]}

Doherty, J. A. ^{[6
]}

Rossing, M. A. ^{[6
]}

Whittemore, A. S. ^{[7
]}

McGuire, V. ^{[7
]}

DiCioccio, R. A. ^{[8
]}

Goodman, M. T. ^{[9
]}

Lurie, G. ^{[9
]}

Carney, M. E. ^{[9
]}

Wilkens, L. R. ^{[9
]}

Ness, R. B. ^{[10
]}

Moysich, K. B. ^{[11
]}

Edwards, R. ^{[12
]}

Jennison, E. ^{[13
]}

Kjaer, S. K. ^{[14
]}

Hogdall, E. ^{[14
]}

Hogdall, C. K. ^{[15
]}

Goode, E. L. ^{[16
]}

Sellers, T. A. ^{[17
]}

Vierkant, R. A. ^{[16
]}

Cunningham, J. C. ^{[16
]}

Schildkraut, J. M. ^{[18
]}

Berchuck, A. ^{[19
]}

Moorman, P. G. ^{[18
]}

Iversen, E. S. ^{[20
]}

Cramer, D. W. ^{[21
]}

Terry, K. L. ^{[21
]}

Vitonis, A. F. ^{[21
]}

Titus-Ernstoff, L. ^{[22
]}

Song, H. ^{[23
]}

Pharoah, P. D. P. ^{[23
]}

Spurdle, A. B. ^{[5
]}

Anton-Culver, H. ^{[24
]}

Ziogas, A. ^{[24
]}

Brewster, W. ^{[25
]}

Galitovskiy, V. ^{[24
]}

机构：

[1] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[2] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48105 USA

[3] UCL, UCL EGA Inst Womens Hlth, Gynaecol Canc Res Labs, London WC1E 6DD, England

[4] Gynaecol Canc Res Ctr, UCL EGA Inst Womens Hlth, London W1T 7DN, England

[5] Post Off Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia

[6] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA

[7] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA

[8] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA

[9] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA

[10] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA

[11] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[12] Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Dept OB GYN RS, Pittsburgh, PA 15213 USA

[13] Gynecol Oncologists NE Ohio, Akron, OH 44302 USA

[14] Danish Canc Soc, Inst Canc Epidemiol, Dept Virus Hormones & Canc, DK-2100 Copenhagen, Denmark

[15] Univ Copenhagen, Rigshosp, Juliane Marie Ctr, Gynaecol Clin, DK-2100 Copenhagen, Denmark

[16] Mayo Clin, Coll Med, Rochester, MN 55905 USA

[17] CANCONT, MRC, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[18] Duke Univ, Med Ctr, Canc Prevent & Control Res Program, Durham, NC 27710 USA

[19] Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA

[20] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA

[21] Brigham & Womens Hosp, Boston, MA 02115 USA

[22] Dartmouth Med Sch, Dept Community & Family Med & Pediat, Lebanon, NH 03756 USA

[23] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England

[24] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA

[25] Chao Clin Canc Ctr, UCI Med Ctr, Dept OB GYN, Orange, CA 92868 USA

[26] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia

来源：

BRITISH JOURNAL OF CANCER | 2009年 / 100卷 / 02期

关键词：

ovarian cancer; genetic susceptibility; oestrogen metabolism; CYP3A4; pooled-analyses; SINGLE-NUCLEOTIDE POLYMORPHISMS; CATECHOL-O-METHYLTRANSFERASE; DNA-REPAIR GENES; COMMON VARIANTS; BREAST-CANCER; CYP3A4; SUSCEPTIBILITY; METABOLISM; CYP17; METAANALYSIS;

D O I：

10.1038/sj.bjc.6604820

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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: OR(homozygous(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, p(het) 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：9

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