Titus Linda, Hatch Elizabeth E, Bertrand Kimberly A, Palmer Julie R, Strohsnitter William C, Huo Dezheng, Curry Michael, Hyer Marianne, Aagaard Kjersti, Gierach Gretchen L, Troisi Rebecca
Department of Pediatrics, Geisel School of Medicine at Dartmouth, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Cancers (Basel). 2024 Jul 18;16(14):2575. doi: 10.3390/cancers16142575.
Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next ("third") generation of offspring.
Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI.
In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36-1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37-32.42). Based on mothers' reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49-1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70-2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported.
To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed.
产前接触己烯雌酚（DES）的女性患宫颈发育异常、乳腺癌以及宫颈/阴道透明细胞腺癌（CCA）的风险升高。产前接触DES的男性患睾丸癌的风险增加。表观遗传变化可能介导DES效应向下一代（“第三代”）后代的传递。
利用第三代女性自我报告的数据，我们评估了DES与癌症以及乳腺和生殖道良性疾病风险的关系。利用产前接触DES和未接触DES的母亲的数据，我们评估了DES与她们的雌性和雄性后代患癌风险的关系。通过标准化发病比（SIR）和95%置信区间（CI）评估癌症风险；通过风险比（HR）和95%CI评估良性和恶性诊断的风险。
在自我报告的数据中，DES暴露与总体癌症（HR 0.83；CI 0.36 - 1.90）、乳腺癌或严重宫颈发育异常的风险增加无关。没有女性报告患CCA。交界性卵巢癌的风险似乎有所升高，但HR不精确（3.46；CI 0.37 - 32.42）。根据母亲的报告，DES暴露并未增加第三代女性患总体癌症（HR 0.80；CI 0.49 - 1.32）或其他癌症的风险。暴露男性的总体癌症风险似乎有所升高（HR 1.41；CI 0.70 - 2.86），但CI范围较宽。暴露男性的睾丸癌风险并未升高；未报告前列腺癌病例。
迄今为止，几乎没有证据表明DES与第三代女性或男性的癌症风险相关，但这些个体相对年轻，需要进一步随访。
