title: Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk.
abstract: 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.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA. cpearce@usc.edu
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moysich
authors.forename: Chris
authors.initials: C
authors.lastname: Hsu
authors.forename: Kara L
authors.initials: KL
authors.lastname: Cushing-Haugen
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
authors.forename: Claus
authors.initials: C
authors.lastname: Hogdall
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Weiva
authors.initials: W
authors.lastname: Sieh
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Medrek
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beesley
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Iversen
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Moorman
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Rossing
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II