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

Publication ,  Journal Article
Pearce, CL; Near, AM; Van Den Berg, DJ; Ramus, SJ; Gentry-Maharaj, A; Menon, U; Gayther, SA; Anderson, AR; Edlund, CK; Wu, AH; Chen, X ...
Published in: Br J Cancer
January 27, 2009

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< or =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.

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Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 27, 2009

Volume

100

Issue

2

Start / End Page

412 / 420

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Middle Aged
  • Humans
  • Homozygote
  • Heterozygote
  • Genotype
 

Citation

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Pearce, C. L., Near, A. M., Van Den Berg, D. J., Ramus, S. J., Gentry-Maharaj, A., Menon, U., … Australian Ovarian Cancer Study Group, . (2009). Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium. Br J Cancer, 100(2), 412–420. https://doi.org/10.1038/sj.bjc.6604820
Pearce, C. L., A. M. Near, D. J. Van Den Berg, S. J. Ramus, A. Gentry-Maharaj, U. Menon, S. A. Gayther, et al. “Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.Br J Cancer 100, no. 2 (January 27, 2009): 412–20. https://doi.org/10.1038/sj.bjc.6604820.
Pearce CL, Near AM, Van Den Berg DJ, Ramus SJ, Gentry-Maharaj A, Menon U, et al. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium. Br J Cancer. 2009 Jan 27;100(2):412–20.
Pearce, C. L., et al. “Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.Br J Cancer, vol. 100, no. 2, Jan. 2009, pp. 412–20. Pubmed, doi:10.1038/sj.bjc.6604820.
Pearce CL, Near AM, Van Den Berg DJ, Ramus SJ, Gentry-Maharaj A, Menon U, Gayther SA, Anderson AR, Edlund CK, Wu AH, Chen X, Beesley J, Webb PM, Holt SK, Chen C, Doherty JA, Rossing MA, Whittemore AS, McGuire V, DiCioccio RA, Goodman MT, Lurie G, Carney ME, Wilkens LR, Ness RB, Moysich KB, Edwards R, Jennison E, Kjaer SK, Hogdall E, Hogdall CK, Goode EL, Sellers TA, Vierkant RA, Cunningham JM, Schildkraut JM, Berchuck A, Moorman PG, Iversen ES, Cramer DW, Terry KL, Vitonis AF, Titus-Ernstoff L, Song H, Pharoah PDP, Spurdle AB, Anton-Culver H, Ziogas A, Brewster W, Galitovskiy V, Chenevix-Trench G, Australian Cancer Study, Australian Ovarian Cancer Study Group. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium. Br J Cancer. 2009 Jan 27;100(2):412–420.

Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 27, 2009

Volume

100

Issue

2

Start / End Page

412 / 420

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Middle Aged
  • Humans
  • Homozygote
  • Heterozygote
  • Genotype