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.
PY - 2011/6
Y1 - 2011/6
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 5 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 5 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.
UR - http://www.scopus.com/inward/record.url?scp=79955993932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955993932&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddr087
DO - 10.1093/hmg/ddr087
M3 - Article
C2 - 21422097
AN - SCOPUS:79955993932
SN - 0964-6906
VL - 20
SP - 2263
EP - 2272
JO - Human molecular genetics
JF - Human molecular genetics
IS - 11
M1 - ddr087
ER -