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Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk.

Publication ,  Journal Article
Pearce, CL; Doherty, JA; Van Den Berg, DJ; Moysich, K; Hsu, C; Cushing-Haugen, KL; Conti, DV; Ramus, SJ; Gentry-Maharaj, A; Menon, U; Song, H ...
Published in: Hum Mol Genet
June 1, 2011

The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases and 5382 additional controls and were able to independently replicate our initial findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81-0.93, P-trend=7.4 × 10(-5)). No heterogeneity of effect across study centers was observed (p(het)=0.25). IGF2 is emerging as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2011

Volume

20

Issue

11

Start / End Page

2263 / 2272

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Middle Aged
  • Insulin-Like Growth Factor II
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor Binding Protein 3
 

Citation

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Pearce, C. L., Doherty, J. A., Van Den Berg, D. J., Moysich, K., Hsu, C., Cushing-Haugen, K. L., … Wu, A. H. (2011). Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk. Hum Mol Genet, 20(11), 2263–2272. https://doi.org/10.1093/hmg/ddr087
Pearce, Celeste Leigh, Jennifer A. Doherty, David J. Van Den Berg, Kirsten Moysich, Chris Hsu, Kara L. Cushing-Haugen, David V. Conti, et al. “Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk.Hum Mol Genet 20, no. 11 (June 1, 2011): 2263–72. https://doi.org/10.1093/hmg/ddr087.
Pearce CL, Doherty JA, Van Den Berg DJ, Moysich K, Hsu C, Cushing-Haugen KL, et al. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk. Hum Mol Genet. 2011 Jun 1;20(11):2263–72.
Pearce, Celeste Leigh, et al. “Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk.Hum Mol Genet, vol. 20, no. 11, June 2011, pp. 2263–72. Pubmed, doi:10.1093/hmg/ddr087.
Pearce CL, Doherty JA, Van Den Berg DJ, Moysich K, Hsu C, Cushing-Haugen KL, Conti DV, Ramus SJ, Gentry-Maharaj A, Menon U, Gayther SA, Pharoah PDP, Song H, Kjaer SK, Hogdall E, Hogdall C, Whittemore AS, McGuire V, Sieh W, Gronwald J, Medrek K, Jakubowska A, Lubinski J, Chenevix-Trench G, AOCS/ACS Study Group, Beesley J, Webb PM, Berchuck A, Schildkraut JM, Iversen ES, Moorman PG, Edlund CK, Stram DO, Pike MC, Ness RB, Rossing MA, Wu AH. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk. Hum Mol Genet. 2011 Jun 1;20(11):2263–2272.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

June 1, 2011

Volume

20

Issue

11

Start / End Page

2263 / 2272

Location

England

Related Subject Headings

  • White People
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Middle Aged
  • Insulin-Like Growth Factor II
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor Binding Protein 3