Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Int J Cancer. 2018 Oct 15;143(8):1858-1867. doi: 10.1002/ijc.31581. Epub 2018 Jul 10.
Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) ≤30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [≥4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), p < 0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.
上皮性卵巢癌是一种病因不明的致命疾病。较高的生育次数与降低卵巢癌风险相关。然而，对于多产妇，妊娠相关因素对风险的影响尚不清楚。这项基于人群的病例对照研究纳入了 1967 年至 2013 年间丹麦、芬兰、挪威和瑞典的所有上皮性卵巢癌多产妇（n=10957）和多达 10 名匹配对照（n=107864）。我们使用条件逻辑回归估计了与组织学亚型相关的妊娠相关因素和卵巢癌风险的比值比（OR）及其 95%置信区间（CI）。早产与风险增加相关[妊娠长度（末次妊娠）≤30 周与 39-41 周，OR 1.33（95%CI 1.06-1.67），调整了分娩次数]；随着妊娠长度的缩短，OR 增加（趋势检验 p<0.001）。首次和末次生育年龄较大与风险降低相关[首次生育：30-39 岁与<25 岁相比：调整后的 OR 0.76（95%CI 0.70-0.83）；末次生育 30-39 岁与<25 岁相比：调整后的 OR 0.76（95%CI 0.71-0.82）]。生育次数增加具有保护作用[≥4 次与 1 次相比：OR 0.63（95%CI 0.59-0.68)]，对于所有亚型均如此，透明细胞肿瘤最为明显[OR 0.30（95%CI 0.21-0.44），p<0.001]。多胎妊娠、子痫前期或胎儿大小与卵巢癌风险无关。总之，除了高生育次数外，足月妊娠和高龄妊娠与卵巢癌风险降低相关。我们的研究结果支持细胞清除假说，即近期妊娠通过胎盘或卵巢激素清除卵巢/输卵管上皮的癌前细胞提供保护。
