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.

中文翻译：

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卵巢癌的风险随着排卵周期数的增加而增加：来自卵巢癌队列联盟 (OC3) 的分析。

在女性的生育年限内，反复暴露于卵巢表面和输卵管远端排卵后的急性促炎环境可能会增加卵巢癌的风险。为了解决这个问题，分析包括来自 20 个前瞻性队列的 558,709 名自然绝经妇女的个人水平数据，其中 3,246 人发展为浸润性上皮性卵巢癌（2,045 名浆液性癌，319 名子宫内膜样癌，184 名粘液性癌，121 名透明细胞癌，577 名其他/未知）。Cox 模型用于估计生命周期排卵周期 (LOC) 及其组成部分之间的多变量调整 HRs 以及总体和组织型的卵巢癌风险。LOC 第 90 个百分位（>514 个周期）的女性被诊断为卵巢癌的可能性几乎是第 10 个百分位（<294）的女性的两倍 [HR（95% 置信区间）：1.92（1.60-2.30）]。LOC（60 个周期）每增加 5 年，风险增加 14% [(1.10-1.17)]；在调整 LOC 组成部分后，这种关联仍然存在：怀孕次数和口服避孕药使用 [1.08 (1.04-1.12)]。相关性因组织型而异，浆液性 [1.13 (1.09-1.17)]、子宫内膜样 [1.20 (1.10-1.32)] 和透明细胞 [1.37 (1.18-1.58)] 的风险增加，但粘液性 [0.99 (0.88- 1.10），P-异质性= 0.01]肿瘤。通过调整 LOC 成分 [1.08 浆液性，1.11 子宫内膜样，1.26 透明细胞，0.94 粘液性]，组织型的异质性降低 [P-异质性 = 0.15]。虽然卵巢癌的 10 年绝对风险很小，但随着 LOC 的数量从大约 300 增加到 500，它大约翻倍。效果的一致性和线性强烈支持这样的假设，即每次排卵都会导致大多数卵巢癌风险的小幅增加，这种风险会在一生中累积，这表明这是确定干预策略的重要领域。意义：虽然卵巢癌很少见，但随着终生排卵周期数从大约 300 增加到 500，大多数卵巢癌的风险会增加一倍。因此，确定癌症预防研究的重要领域。