Journal Article

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

Celeste Leigh Pearce, Jennifer A. Doherty, David J. Van Den Berg, Kirsten Moysich, Chris Hsu, Kara L. Cushing-Haugen, David V. Conti, Susan J. Ramus, Aleksandra Gentry-Maharaj, Usha Menon, Simon A. Gayther, Paul D.P. Pharoah, Honglin Song, Susanne K. Kjaer, Estrid Hogdall, Claus Hogdall, Alice S. Whittemore, Valerie McGuire, Weiva Sieh, Jacek Gronwald, Krzysztof Medrek, Anna Jakubowska, Jan Lubinski, Georgia Chenevix-Trench, Jonathan Beesley, Penelope M. Webb, Andrew Berchuck, Joellen M. Schildkraut, Edwin S. Iversen, Patricia G. Moorman, Christopher K. Edlund, Daniel O. Stram, Malcolm C. Pike, Roberta B. Ness, Mary Anne Rossing and Anna H. Wu

in Human Molecular Genetics

Volume 20, issue 11, pages 2263-2272
Published in print June 2011 | ISSN: 0964-6906
Published online March 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr087
Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

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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 (phet=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.

Journal Article.  5654 words.  Illustrated.

Subjects: Genetics and Genomics

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