Combined and interactive effects of environmental and gwas-identified risk factors in ovarian cancer

Pearce C.L., Rossing M.A., Lee A.W., Ness R.B., Webb P.M., Chenevix-Trench G., Jordan S.M., Stram D.A., Chang-Claude J., Hein R., Nickels S., Lurie G., Thompson P.J., Carney M.E., Goodman M.T., Moysich K., Hogdall E., Jensen A., Goode E.L., Fridley B.L., Cunningham J.M., Vierkant R.A., Weber R.P., Ziogas A., Anton-Culver H., Gayther S.A., Gentry-Maharaj A., Menon U., Ramus S.J., Brinton L., Wentzensen N., Lissowska J., Garcia-Closas M., Massuger L.F.A.G., Kiemeney L.A.L.M., Van Altena A.M., Aben K.K.H., Berchuck A., Doherty J.A., Iversen E., Mcguire V., Moorman P.G., Pharoah P., Pike M.C., Risch H., Sieh W., Stram D.O., Terry K.L., Whittemore A., Wu A.H., Schildkraut J.M. and Kjaer S.K. (2013) Combined and interactive effects of environmental and gwas-identified risk factors in ovarian cancer. Cancer Epidemiology Biomarkers and Prevention, 22 5: 880-890. doi:10.1158/1055-9965.EPI-12-1030-T

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Author Pearce C.L.
Rossing M.A.
Lee A.W.
Ness R.B.
Webb P.M.
Chenevix-Trench G.
Jordan S.M.
Stram D.A.
Chang-Claude J.
Hein R.
Nickels S.
Lurie G.
Thompson P.J.
Carney M.E.
Goodman M.T.
Moysich K.
Hogdall E.
Jensen A.
Goode E.L.
Fridley B.L.
Cunningham J.M.
Vierkant R.A.
Weber R.P.
Ziogas A.
Anton-Culver H.
Gayther S.A.
Gentry-Maharaj A.
Menon U.
Ramus S.J.
Brinton L.
Wentzensen N.
Lissowska J.
Garcia-Closas M.
Massuger L.F.A.G.
Kiemeney L.A.L.M.
Van Altena A.M.
Aben K.K.H.
Berchuck A.
Doherty J.A.
Iversen E.
Mcguire V.
Moorman P.G.
Pharoah P.
Pike M.C.
Risch H.
Sieh W.
Stram D.O.
Terry K.L.
Whittemore A.
Wu A.H.
Schildkraut J.M.
Kjaer S.K.
Title Combined and interactive effects of environmental and gwas-identified risk factors in ovarian cancer
Journal name Cancer Epidemiology Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-12-1030-T
Volume 22
Issue 5
Start page 880
End page 890
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Subject 2713 Epidemiology
2730 Oncology
Abstract Background: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied. Methods: Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic 'risk score' was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk. Results: Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48-1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet > 0.001), parity (Phet > 0.01), and tubal ligation (Phet = 0.041). Conclusions: The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted. Cancer Epidemiol Biomarkers Prev; 22(5); 880-90.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Created: Wed, 02 Apr 2014, 00:21:34 EST by Matthew Lamb on behalf of School of Medicine