Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Centre for Women's Mental Health during the Reproductive Lifespan - WoMHeR, Uppsala University, Uppsala, Sweden.
Cancer Res. 2021 Feb 15;81(4):1153-1162. doi: 10.1158/0008-5472.CAN-20-2476. Epub 2020 Dec 17.
Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the OR, and instantaneous risk, as measured by the HR, were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer [OR = 0.72; 95% confidence interval (CI), 0.65-0.81] and endometrial cancer (OR = 0.68; 95% CI, 0.62-0.75), an association that was stronger with longer use ( < 0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age (OR = 1.10; 95% CI, 1.03-1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR = 1.55; 95% CI, 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited. SIGNIFICANCE: These results enable women and physicians to make more informed decisions considering oral contraceptive use, thus constituting an important step toward personalized medicine.
口服避孕药的使用被认为会影响乳腺癌、卵巢癌和子宫内膜癌的风险。本研究的目的是阐明长期口服避孕药使用与癌症风险之间的时依关系。我们对英国生物库中的 256661 名女性进行了一项观察性研究，这些女性出生于 1939 年至 1970 年之间。通过自我报告的数据和国家登记册，在 2019 年 3 月之前收集癌症诊断信息。使用 Logistic 和 Cox 回归分析分别评估研究期间癌症累积风险（通过 OR 衡量）和瞬时风险（通过 HR 衡量）。与从不使用者相比，曾使用者的卵巢癌（OR=0.72；95%置信区间[CI]，0.65-0.81）和子宫内膜癌（OR=0.68；95%CI，0.62-0.75）的风险较低，这种关联随着使用时间的延长而增强（<0.001）。在限制随访时间为 55 岁时，发现乳腺癌的患病风险在女性中增加（OR=1.10；95%CI，1.03-1.17），但在整个随访期间则不然。我们仅发现停药后≤2 年内，前使用者的乳腺癌 HR 更高（HR=1.55；95%CI，1.06-2.28），而对卵巢癌和子宫内膜癌的保护关联在停药后长达 35 年仍显著。鉴于本研究中提供的证据，我们认为口服避孕药可以显著降低女性患卵巢癌和子宫内膜癌的风险，而它们对乳腺癌终身风险的影响则有限。意义：这些结果使女性和医生能够在考虑使用口服避孕药时做出更明智的决策，从而朝着个性化医学迈出了重要的一步。
