Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study

Lee, A. W. et al. (2015) Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study. Gynecologic Oncology, 136(3), pp. 542-548. (doi:10.1016/j.ygyno.2014.12.017) (PMID:25528498)

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Abstract

Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted.<p></p> Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations.<p></p> Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive).<p></p> Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Paul, Mr James and Carty, Mrs Karen and Mcneish, Professor Iain
Authors: Lee, A. W., Tyrer, J. P., Doherty, J. A., Stram, D. A., Kupryjanczyk, J., Dansonka-Mieszkowska, A., Plisiecka-Halasa, J., Spiewankiewicz, B., Myers, E. J., Chenevix-Trench, G., Fasching, P. A., Beckmann, M. W., Ekici, A. B., Hein, A., Vergote, I., Van Nieuwenhuysen, E., Lambrechts, D., Wicklund, K. G., Eilber, U., Wang-Gohrke, S., Chang-Claude, J., Rudolph, A., Sucheston-Campbell, L., Odunsi, K., Moysich, K. B., Shvetsov, Y. B., Thompson, P. J., Goodman, M. T., Wilkens, L. R., Dörk, T., Hillemanns, P., Dürst, M., Runnebaum, I. B., Bogdanova, N., Pelttari, L. M., Nevanlinna, H., Leminen, A., Edwards, R. P., Kelley, J. L., Harter, P., Schwaab, I., Heitz, F., du Bois, A., Orsulic, S., Lester, J., Walsh, C., Karlan, B. Y., Hogdall, E., Kjaer, S. K., Jensen, A., Vierkant, R. A., Cunningham, J. M., Goode, E. L., Fridley, B. L., Southey, M. C., Giles, G. G., Bruinsma, F., Wu, X., Hildebrandt, M. A.T., Lu, K., Liang, D., Bisogna, M., Levine, D. A., Weber, R. P., Schildkraut, J. M., Iversen, E. S., Berchuck, A., Terry, K. L., Cramer, D. W., Tworoger, S. S., Poole, E. M., Olson, S. H., Orlow, I., Bandera, E. V., Bjorge, L., Tangen, I. L., Salvesen, H. B., Krakstad, C., Massuger, L. F.A.G., Kiemeney, L. A., Aben, K. K.H., van Altena, A. M., Bean, Y., Pejovic, T., Kellar, M., Le, N. D., Cook, L. S., Kelemen, L. E., Brooks-Wilson, A., Lubinski, J., Gronwald, J., Cybulski, C., Jakubowska, A., Wentzensen, N., Brinton, L. A., Lissowska, J., Yang, H., Nedergaard, L., Lundvall, L., Hogdall, C., Song, H., Campbell, I. G., Eccles, D., Glasspool, R., Siddiqui, N., Carty, K., Paul, J., Mcneish, I., Sieh, W., McGuire, V., Rothstein, J. H., Whittemore, A. S., McLaughlin, J. R., Risch, H. A., Phelan, C. M., Anton-Culver, H., Ziogas, A., Menon, U., Ramus, S. J., Gentry-Maharaj, A., Harrington, P., Pike, M. C., Modugno, F., Rossing, M. A., Ness, R. B., Pharoah, P. D.P., Stram, D. O., Wu, A. H., and Pearce, C. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Gynecologic Oncology
Publisher:Elsevier
ISSN:0090-8258
ISSN (Online):1095-6859

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