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; Anna H Wu; AOCS/ACS Study Group

doi:10.1093/hmg/ddr087

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 GronwaldKrzysztof 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, Anna H Wu, AOCS/ACS Study Group

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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 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.

Originalsprog	Engelsk
Tidsskrift	Human Molecular Genetics
Vol/bind	20
Udgave nummer	11
Sider (fra-til)	2263-72
Antal sider	10
ISSN	0964-6906
DOI	https://doi.org/10.1093/hmg/ddr087 https://doi.org/10.1093/hmg/ddr087
Status	Udgivet - 1 jun. 2011

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Pearce, C. L., Doherty, J. A., Van Den Berg, D. J., Moysich, K., Hsu, C., Cushing-Haugen, K. L., Conti, D. V., Ramus, S. J., Gentry-Maharaj, A., Menon, U., Gayther, S. A., Pharoah, P. D. P., Song, H., Kjaer, S. K., Hogdall, E., Hogdall, C., Whittemore, A. S., McGuire, V., Sieh, W., ... AOCS/ACS Study Group (2011). Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk. Human Molecular Genetics, 20(11), 2263-72. https://doi.org/10.1093/hmg/ddr087, https://doi.org/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, Beesley, J, Webb, PM, Berchuck, A, Schildkraut, JM, Iversen, ES, Moorman, PG, Edlund, CK, Stram, DO, Pike, MC, Ness, RB, Rossing, MA, Wu, AH & AOCS/ACS Study Group 2011, 'Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk', Human Molecular Genetics, bind 20, nr. 11, s. 2263-72. https://doi.org/10.1093/hmg/ddr087, https://doi.org/10.1093/hmg/ddr087

@article{a79844fbcacf4346af8977a76a55bd9f,

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 (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.",

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

year = "2011",

month = jun,

day = "1",

doi = "10.1093/hmg/ddr087",

language = "English",

volume = "20",

pages = "2263--72",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "11",

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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 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.

U2 - 10.1093/hmg/ddr087

DO - 10.1093/hmg/ddr087

M3 - Journal article

C2 - 21422097

SN - 0964-6906

VL - 20

SP - 2263

EP - 2272

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 11

ER -

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

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