Guoqiao Zheng

Role of pre-diagnostic reproductive factors on long-term (10 years or greater) survival of epithelial ovarian cancer: The Extreme study

Several reproductive factors are associated with ovarian cancer risk but the association with survival is less clear. The main aim was to examine the impact of pre-diagnostic reproductive factors on long-term ovarian cancer survival (≥10 years). We included all women with epithelial ovarian cancer in Denmark, 1990-2014. Information on reproductive factors and covariates were obtained from nationwide registers. Using pseudo-values, we estimated the absolute and relative 10-year survival probabilities and 95% CIs for each reproductive factor and ovarian cancer overall, restricted to serous tumors and stratified into localized and non-localized tumors. A relative survival probability >1 indicates better survival. Adjusted models considered age, diagnosis year, histology, stage, comorbidity, and income. In a sub-population sensitivity analysis, we also adjusted for residual disease. The cohort comprised 11,870 women. In the adjusted models, pre-diagnostic parity (relative survival probability 1.08, 95% CI 1.01 to 1.16) and endometriosis (relative survival probability 1.17, 95% CI 1.02 to 1.34) increased the likelihood of surviving ≥10 years in women with localized cancer. Previous infertility also improved the 10-year survival in women with localized ovarian cancer (relative survival probability 1.18, 95% CI 1.07 to 1.29) and in women with a non-localized tumor (relative survival probability 1.45, 95% CI 1.15 to 1.84). Pre-diagnostic pelvic inflammatory disease enhanced 10-year survival in women with localized serous (relative survival probability 1.24, 95% CI 1.03 to 1.49) and non-localized cancer (relative survival probability 1.35, 95% CI 1.04 to 1.76). Previous tubal ligation or hysterectomy were not significantly associated with 10-year survival. Adjustment for residual disease did not substantially change estimates, except for parity and pelvic inflammatory disease, where the associations disappeared. Pre-diagnostic reproductive factors, such as endometriosis or infertility, were associated with improved long-term survival. However, causality cannot be established in this observational study, and more research to confirm our findings and into potential mechanisms is warranted.

Low-dose aspirin use and risk of ovarian cancer: a combined analysis from two nationwide studies in Denmark and Sweden

Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors. In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated. Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204). Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

Ovarian cancer risk factors in relation to family history

Abstract Background Women with a family history of breast and/or ovarian cancer have an increased ovarian cancer risk. Yet it remains uncertain if common ovarian cancer risk factors—especially those that are modifiable—affect this high-risk population similarly to the general population. Methods Using the Danish and Swedish nationwide registers, we established 2 nested case-control study populations in women with a family history of breast and/or ovarian cancer (2138 ovarian cancers, 85 240 controls) and women without (10 730 ovarian cancers, 429 200 controls). The overall and histology-specific associations were assessed with conditional logistic regression. The country-specific estimates were combined based on a fixed-effect assumption. Results Multiparity, hysterectomy, tubal ligation, salpingectomy, and oral contraceptive (OC) use were associated with a reduced risk of ovarian cancer in women with and without a family history, while endometriosis and menopausal hormone therapy were associated with increased risk. Multiparity and OC use presented protective effects across all histologic subtypes except mucinous ovarian cancer, which was not associated with OC use. Menopausal hormone treatment increased the risk of serous ovarian cancer but decreased the risk of the mucinous and clear cell cancers. Endometriosis was especially related to an increased risk of endometrioid and clear cell ovarian cancer. Conclusion Factors associated with a decreased ovarian cancer risk were similar between women with and without a family history of breast and/or ovarian cancer. Given the higher baseline risk for women with a family history, special attention should be paid to risk factors like endometriosis and nulliparity in this high-risk population.

Prediagnostic use of menopausal hormone therapy and long‐term survival of localized epithelial ovarian cancer: The Extreme study

AbstractUse of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long‐term MHT use, especially estrogen therapy (ET), was associated with improved long‐term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long‐term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000–2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo‐values, 5‐ and 10‐year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5‐year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10‐year survival. Use of MHT was not significantly associated with an improved 5‐ or 10‐year survival in women with localized EOC (5‐year relative survival probability = 0.95, 95% CI: 0.89–1.02; 10‐year relative survival probability = 0.92, 95% CI: 0.84–1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long‐term survival of localized EOC.

Paracetamol use and risk of epithelial ovarian cancer: A nationwide nested case–control study

AbstractObjectiveTo investigate whether paracetamol use is associated with a reduced risk of epithelial ovarian cancer (EOC).DesignA nationwide nested case–control study.SettingDanish female population.PopulationA total of 9589 EOC cases diagnosed from 2000 to 2019 were age‐matched with 383 549 randomly selected female controls using risk set sampling.MethodsParacetamol use, reproductive history, history of medication and history of surgery were retrieved from Danish national registers. Paracetamol use was defined as at least two prescriptions for up to 1 year before the index date, and was further classified according to recency, duration, cumulative dose and intensity of dose.Main outcome measuresConditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between paracetamol and EOC risk, overall and by histological subtypes.Results‘Ever’ use of paracetamol was associated with a reduced EOC risk after adjusting for potential confounding factors (OR 0.92, 95% CI 0.87–0.97). The association was only significant among recent users (OR 0.89, 95% CI 0.84–0.95). The risk declined further with the increasing level of cumulative dose and intensity; women from the group with a high cumulative dose and a high intensity had a 13% (OR 0.87, 95% CI 0.80–0.94) and 14% (OR 0.86, 95% CI 0.79–0.93) reduced risk, respectively. In the histological subtype analysis, reduced risk with ‘ever’ use was most pronounced for serous and clear cell tumours.ConclusionsParacetamol use was associated with a decreased risk of EOC in a dose–response manner. Future studies are needed to validate the findings and investigate the mechanisms behind the association.