The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3).

View/ Open
Date
2020-03Author
Trabert, B
Tworoger, SS
O'Brien, KM
Townsend, MK
Fortner, RT
Iversen, ES
Hartge, P
White, E
Amiano, P
Arslan, AA
Bernstein, L
Brinton, LA
Buring, JE
Dossus, L
Fraser, GE
Gaudet, MM
Giles, GG
Gram, IT
Harris, HR
Bolton, JH
Idahl, A
Jones, ME
Kaaks, R
Kirsh, VA
Knutsen, SF
Kvaskoff, M
Lacey, JV
Lee, I-M
Milne, RL
Onland-Moret, NC
Overvad, K
Patel, AV
Peters, U
Poynter, JN
Riboli, E
Robien, K
Rohan, TE
Sandler, DP
Schairer, C
Schouten, LJ
Setiawan, VW
Swerdlow, AJ
Travis, RC
Trichopoulou, A
van den Brandt, PA
Visvanathan, K
Wilkens, LR
Wolk, A
Zeleniuch-Jacquotte, A
Wentzensen, N
Ovarian Cancer Cohort Consortium (OC3)
Type
Journal Article
Metadata
Show full item recordAbstract
Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.
Collections
Subject
Ovarian Cancer Cohort Consortium (OC3)
Fallopian Tubes
Ovary
Humans
Ovarian Neoplasms
Contraceptive Agents
Reproductive History
Proportional Hazards Models
Risk Assessment
Risk Factors
Prospective Studies
Ovulation
Aged
Middle Aged
Female
Research team
Aetiological Epidemiology
Language
eng
Date accepted
2020-01-09
License start date
2020-03
Citation
Cancer research, 2020, 80 (5), pp. 1210 - 1218
Related items
Showing items related by title, author, creator and subject.
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2; Hollestelle, A; van der Baan, FH; Berchuck, A; Johnatty, SE; et al. (2016-05)Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer ... -
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.
Lawrenson, K; Kar, S; McCue, K; Kuchenbaeker, K; Michailidou, K; et al. (2016-09-07)A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify ... -
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
Michailidou, K; Hall, P; Gonzalez-Neira, A; Ghoussaini, M; Dennis, J; et al. (2013-04)Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We ...