Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21...

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Main Authors: Fortner, RT, Poole, EM, Wentzensen, NA, Trabert, B, White, E, Arslan, AA, Patel, AV, Setiawan, VW, Visvanathan, K, Weiderpass, E, Adami, H-O, Black, A, Bernstein, L, Brinton, LA, Buring, J, Clendenen, TV, Fournier, A, Fraser, G, Gapstur, SM, Gaudet, MM, Giles, GG, Gram, IT, Hartge, P, Hoffman-Bolton, J, Idahl, A, Kaaks, R, Kirsh, VA, Knutsen, S, Koh, W-P, Lacey, JV, Lee, I-M, Lundin, E, Merritt, MA, Milne, RL, Onland-Moret, NC, Peters, U, Poynter, JN, Rinaldi, S, Robien, K, Rohan, T, Sánchez, M-J, Schairer, C, Schouten, LJ, Tjonneland, A, Townsend, MK, Travis, RC, Trichopoulou, A, Van Den Brandt, PA, Vineis, P, Wilkens, L, Wolk, A, Yang, HP, Zeleniuch-Jacquotte, A, Tworoger, SS
Format: Journal article
Language:English
Published: Wiley 2019
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author Fortner, RT
Poole, EM
Wentzensen, NA
Trabert, B
White, E
Arslan, AA
Patel, AV
Setiawan, VW
Visvanathan, K
Weiderpass, E
Adami, H-O
Black, A
Bernstein, L
Brinton, LA
Buring, J
Clendenen, TV
Fournier, A
Fraser, G
Gapstur, SM
Gaudet, MM
Giles, GG
Gram, IT
Hartge, P
Hoffman-Bolton, J
Idahl, A
Kaaks, R
Kirsh, VA
Knutsen, S
Koh, W-P
Lacey, JV
Lee, I-M
Lundin, E
Merritt, MA
Milne, RL
Onland-Moret, NC
Peters, U
Poynter, JN
Rinaldi, S
Robien, K
Rohan, T
Sánchez, M-J
Schairer, C
Schouten, LJ
Tjonneland, A
Townsend, MK
Travis, RC
Trichopoulou, A
Van Den Brandt, PA
Vineis, P
Wilkens, L
Wolk, A
Yang, HP
Zeleniuch-Jacquotte, A
Tworoger, SS
author_facet Fortner, RT
Poole, EM
Wentzensen, NA
Trabert, B
White, E
Arslan, AA
Patel, AV
Setiawan, VW
Visvanathan, K
Weiderpass, E
Adami, H-O
Black, A
Bernstein, L
Brinton, LA
Buring, J
Clendenen, TV
Fournier, A
Fraser, G
Gapstur, SM
Gaudet, MM
Giles, GG
Gram, IT
Hartge, P
Hoffman-Bolton, J
Idahl, A
Kaaks, R
Kirsh, VA
Knutsen, S
Koh, W-P
Lacey, JV
Lee, I-M
Lundin, E
Merritt, MA
Milne, RL
Onland-Moret, NC
Peters, U
Poynter, JN
Rinaldi, S
Robien, K
Rohan, T
Sánchez, M-J
Schairer, C
Schouten, LJ
Tjonneland, A
Townsend, MK
Travis, RC
Trichopoulou, A
Van Den Brandt, PA
Vineis, P
Wilkens, L
Wolk, A
Yang, HP
Zeleniuch-Jacquotte, A
Tworoger, SS
author_sort Fortner, RT
collection OXFORD
description Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
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spelling oxford-uuid:e2b34081-63b3-40cd-8229-c9fe553135be2022-03-27T10:03:48ZOvarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort ConsortiumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e2b34081-63b3-40cd-8229-c9fe553135beEnglishSymplectic Elements at OxfordWiley2019Fortner, RTPoole, EMWentzensen, NATrabert, BWhite, EArslan, AAPatel, AVSetiawan, VWVisvanathan, KWeiderpass, EAdami, H-OBlack, ABernstein, LBrinton, LABuring, JClendenen, TVFournier, AFraser, GGapstur, SMGaudet, MMGiles, GGGram, ITHartge, PHoffman-Bolton, JIdahl, AKaaks, RKirsh, VAKnutsen, SKoh, W-PLacey, JVLee, I-MLundin, EMerritt, MAMilne, RLOnland-Moret, NCPeters, UPoynter, JNRinaldi, SRobien, KRohan, TSánchez, M-JSchairer, CSchouten, LJTjonneland, ATownsend, MKTravis, RCTrichopoulou, AVan Den Brandt, PAVineis, PWilkens, LWolk, AYang, HPZeleniuch-Jacquotte, ATworoger, SSOvarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
spellingShingle Fortner, RT
Poole, EM
Wentzensen, NA
Trabert, B
White, E
Arslan, AA
Patel, AV
Setiawan, VW
Visvanathan, K
Weiderpass, E
Adami, H-O
Black, A
Bernstein, L
Brinton, LA
Buring, J
Clendenen, TV
Fournier, A
Fraser, G
Gapstur, SM
Gaudet, MM
Giles, GG
Gram, IT
Hartge, P
Hoffman-Bolton, J
Idahl, A
Kaaks, R
Kirsh, VA
Knutsen, S
Koh, W-P
Lacey, JV
Lee, I-M
Lundin, E
Merritt, MA
Milne, RL
Onland-Moret, NC
Peters, U
Poynter, JN
Rinaldi, S
Robien, K
Rohan, T
Sánchez, M-J
Schairer, C
Schouten, LJ
Tjonneland, A
Townsend, MK
Travis, RC
Trichopoulou, A
Van Den Brandt, PA
Vineis, P
Wilkens, L
Wolk, A
Yang, HP
Zeleniuch-Jacquotte, A
Tworoger, SS
Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title_full Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title_fullStr Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title_full_unstemmed Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title_short Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium
title_sort ovarian cancer risk factors by tumor aggressiveness an analysis from the ovarian cancer cohort consortium
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