TY - JOUR

T1 - Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

AU - Pearce, Celeste Leigh

AU - Doherty, Jennifer A

AU - Van Den Berg, David J

AU - Moysich, Kirsten

AU - Hsu, Chris

AU - Cushing-Haugen, Kara L

AU - Conti, David V

AU - Ramus, Susan J

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Gayther, Simon A

AU - Pharoah, Paul D P

AU - Song, Honglin

AU - Kjaer, Susanne K

AU - Hogdall, Estrid

AU - Hogdall, Claus

AU - Whittemore, Alice S

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Gronwald, Jacek

AU - Medrek, Krzysztof

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Webb, Penelope M

AU - Berchuck, Andrew

AU - Schildkraut, Joellen M

AU - Iversen, Edwin S

AU - Moorman, Patricia G

AU - Edlund, Christopher K

AU - Stram, Daniel O

AU - Pike, Malcolm C

AU - Ness, Roberta B

AU - Rossing, Mary Anne

AU - Wu, Anna H

AU - AOCS/ACS Study Group

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddr087

DO - 10.1093/hmg/ddr087

M3 - Journal article

C2 - 21422097

VL - 20

SP - 2263

EP - 2272

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 11

ER -