Skip to main content

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

Publication ,  Journal Article
Pearce, CL; Rossing, MA; Lee, AW; Ness, RB; Webb, PM; for Australian Cancer Study (Ovarian Cancer), ; Australian Ovarian Cancer Study Group, ...
Published in: Cancer Epidemiol Biomarkers Prev
May 2013

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

May 2013

Volume

22

Issue

5

Start / End Page

880 / 890

Location

United States

Related Subject Headings

  • Risk Factors
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene-Environment Interaction
  • Female
  • Epidemiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pearce, C. L., Rossing, M. A., Lee, A. W., Ness, R. B., Webb, P. M., for Australian Cancer Study (Ovarian Cancer), ., … Ovarian Cancer Association Consortium, . (2013). Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer Epidemiol Biomarkers Prev, 22(5), 880–890. https://doi.org/10.1158/1055-9965.EPI-12-1030-T
Pearce, Celeste Leigh, Mary Anne Rossing, Alice W. Lee, Roberta B. Ness, Penelope M. Webb, Penelope M. for Australian Cancer Study (Ovarian Cancer), Penelope M. Australian Ovarian Cancer Study Group, et al. “Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.Cancer Epidemiol Biomarkers Prev 22, no. 5 (May 2013): 880–90. https://doi.org/10.1158/1055-9965.EPI-12-1030-T.
Pearce CL, Rossing MA, Lee AW, Ness RB, Webb PM, for Australian Cancer Study (Ovarian Cancer), et al. Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):880–90.
Pearce, Celeste Leigh, et al. “Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.Cancer Epidemiol Biomarkers Prev, vol. 22, no. 5, May 2013, pp. 880–90. Pubmed, doi:10.1158/1055-9965.EPI-12-1030-T.
Pearce CL, Rossing MA, Lee AW, Ness RB, Webb PM, for Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Chenevix-Trench G, Jordan SM, Stram DA, Chang-Claude J, Hein R, Nickels S, Lurie G, Thompson PJ, Carney ME, Goodman MT, Moysich K, Hogdall E, Jensen A, Goode EL, Fridley BL, Cunningham JM, Vierkant RA, Weber RP, Ziogas A, Anton-Culver H, Gayther SA, Gentry-Maharaj A, Menon U, Ramus SJ, Brinton L, Wentzensen N, Lissowska J, Garcia-Closas M, Massuger LFAG, Kiemeney LALM, Van Altena AM, Aben KKH, Berchuck A, Doherty JA, Iversen E, McGuire V, Moorman PG, Pharoah P, Pike MC, Risch H, Sieh W, Stram DO, Terry KL, Whittemore A, Wu AH, Schildkraut JM, Kjaer SK, Ovarian Cancer Association Consortium. Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):880–890.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

May 2013

Volume

22

Issue

5

Start / End Page

880 / 890

Location

United States

Related Subject Headings

  • Risk Factors
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene-Environment Interaction
  • Female
  • Epidemiology