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

Celeste Leigh Pearce; Mary Anne Rossing; Alice W Lee; Roberta B Ness; Penelope M Webb; Georgia Chenevix-Trench; Susan M Jordan; Douglas A Stram; Jenny Chang-Claude; Rebecca Hein; Stefan Nickels; Galina Lurie; Pamela J Thompson; Michael E Carney; Marc T Goodman; Kirsten Moysich; Estrid Hogdall; Allan Jensen; Ellen L Goode; Brooke L Fridley; Julie M Cunningham; Robert A Vierkant; Rachel Palmieri Weber; Argyrios Ziogas; Hoda Anton-Culver; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Susan J Ramus; Louise Brinton; Nicolas Wentzensen; Jolanta Lissowska; Montserrat Garcia-Closas; Leon F A G Massuger; Lambertus A L M Kiemeney; Anne M Van Altena; Katja K H Aben; Andrew Berchuck; Jennifer A Doherty; Edwin Iversen; Valerie McGuire; Patricia G Moorman; Paul Pharoah; Malcolm C Pike; Harvey Risch; Weiva Sieh; Daniel O Stram; Kathryn L Terry; Alice Whittemore; Anna H Wu; Joellen M Schildkraut; Susanne K Kjaer; for Australian Cancer Study (Ovarian Cancer)

doi:10.1158/1055-9965.EPI-12-1030-T

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

Celeste Leigh Pearce, Mary Anne Rossing, Alice W Lee, Roberta B Ness, Penelope M Webb, Georgia Chenevix-Trench, Susan M Jordan, Douglas A Stram, Jenny Chang-Claude, Rebecca Hein, Stefan Nickels, Galina Lurie, Pamela J Thompson, Michael E Carney, Marc T Goodman, Kirsten Moysich, Estrid Hogdall, Allan Jensen, Ellen L Goode, Brooke L FridleyJulie M Cunningham, Robert A Vierkant, Rachel Palmieri Weber, Argyrios Ziogas, Hoda Anton-Culver, Simon A Gayther, Aleksandra Gentry-Maharaj, Usha Menon, Susan J Ramus, Louise Brinton, Nicolas Wentzensen, Jolanta Lissowska, Montserrat Garcia-Closas, Leon F A G Massuger, Lambertus A L M Kiemeney, Anne M Van Altena, Katja K H Aben, Andrew Berchuck, Jennifer A Doherty, Edwin Iversen, Valerie McGuire, Patricia G Moorman, Paul Pharoah, Malcolm C Pike, Harvey Risch, Weiva Sieh, Daniel O Stram, Kathryn L Terry, Alice Whittemore, Anna H Wu, Joellen M Schildkraut, Susanne K Kjaer, for Australian Cancer Study (Ovarian Cancer)

37 Citations (Scopus)

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.

Original language	English
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	22
Issue number	5
Pages (from-to)	880-890
Number of pages	11
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-12-1030-T
Publication status	Published - May 2013

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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., ... Cancer), F. A. C. S. (2013). Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 22(5), 880-890. https://doi.org/10.1158/1055-9965.EPI-12-1030-T

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. / Pearce, Celeste Leigh; Rossing, Mary Anne; Lee, Alice W et al.

In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 22, No. 5, 05.2013, p. 880-890.

Research output: Contribution to journal › Journal article › Research › peer-review

Pearce, CL, Rossing, MA, Lee, AW, Ness, RB, Webb, PM, 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 & Cancer), FACS 2013, 'Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 22, no. 5, pp. 880-890. https://doi.org/10.1158/1055-9965.EPI-12-1030-T

Pearce CL, Rossing MA, Lee AW, Ness RB, Webb PM, Chenevix-Trench G et al. Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2013 May;22(5):880-890. doi: 10.1158/1055-9965.EPI-12-1030-T

Pearce, Celeste Leigh ; Rossing, Mary Anne ; Lee, Alice W et al. / Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer. In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2013 ; Vol. 22, No. 5. pp. 880-890.

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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.",

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T1 - Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer

AU - Pearce, Celeste Leigh

AU - Rossing, Mary Anne

AU - Lee, Alice W

AU - Ness, Roberta B

AU - Webb, Penelope M

AU - Chenevix-Trench, Georgia

AU - Jordan, Susan M

AU - Stram, Douglas A

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Nickels, Stefan

AU - Lurie, Galina

AU - Thompson, Pamela J

AU - Carney, Michael E

AU - Goodman, Marc T

AU - Moysich, Kirsten

AU - Hogdall, Estrid

AU - Jensen, Allan

AU - Goode, Ellen L

AU - Fridley, Brooke L

AU - Cunningham, Julie M

AU - Vierkant, Robert A

AU - Weber, Rachel Palmieri

AU - Ziogas, Argyrios

AU - Anton-Culver, Hoda

AU - Gayther, Simon A

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Ramus, Susan J

AU - Brinton, Louise

AU - Wentzensen, Nicolas

AU - Lissowska, Jolanta

AU - Garcia-Closas, Montserrat

AU - Massuger, Leon F A G

AU - Kiemeney, Lambertus A L M

AU - Van Altena, Anne M

AU - Aben, Katja K H

AU - Berchuck, Andrew

AU - Doherty, Jennifer A

AU - Iversen, Edwin

AU - McGuire, Valerie

AU - Moorman, Patricia G

AU - Pharoah, Paul

AU - Pike, Malcolm C

AU - Risch, Harvey

AU - Sieh, Weiva

AU - Stram, Daniel O

AU - Terry, Kathryn L

AU - Whittemore, Alice

AU - Wu, Anna H

AU - Schildkraut, Joellen M

AU - Kjaer, Susanne K

AU - Cancer), for Australian Cancer Study (Ovarian

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-12-1030-T

DO - 10.1158/1055-9965.EPI-12-1030-T

M3 - Journal article

C2 - 23462924

SN - 1055-9965

VL - 22

SP - 880

EP - 890

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 5

ER -

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

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