Abstract
In utero exposure to diethylstilbestrol (DES) is associated with increased risk of clear cell adenocarcinoma (CCAC) of the vagina or cervix. It is not clear whether these risks remain increased at older ages, and if the risks of other cancer sites, including breast cancer, are increased. This nationwide cohort study included 12,249 DES-exposed women and 2,070 unexposed sisters. Hormone-related risk factors and medical history were assessed through questionnaires, and cancer incidence through linkages with nationwide registries. Comparison with general population rates showed no difference in overall cancer risk (SIR = 0.98, 95%CI 0.93-1.04) or breast cancer risk (SIR = 1.03, 95%CI 0.96-1.11) for DES-exposed women. The rate of vaginal cancer was strongly increased for DES-exposed women (SIR = 10.5, 95%CI 5.72-17.6) and was increased in all age categories, including age 60-69 years (SIR = 8.3, 95%CI 1.00-29.9). Risks of both CCAC (SIR = 49.1, 95%CI 21.2-96.8) and squamous cell carcinoma (SCC; SIR = 5.86, 95%CI 2.15-12.8) of the vagina were significantly elevated. When comparing DES-exposed women with DES-unexposed sisters, overall cancer risk and risk of breast cancer were similar (HR = 0.93, 95%CI 0.78-1.11 and HR = 0.97, 95%CI 0.76-1.23, respectively). Apart from the established increased risk of vaginal cancer, women exposed to DES in utero do not seem to be at increased risk of cancer, including breast cancer. The risk of vaginal cancer remains increased also for women in their fifties/sixties. Moreover, the increased risk of vaginal cancer was seen for both subtypes CCAC and SCC. Screening for vaginal cancer up to higher ages than currently recommended (< 60 years) should be considered.