| 1. |
- Hathaway, Cassandra A., et al.
(författare)
-
Prolactin and risk of epithelial ovarian cancer
- 2021
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 30:9, s. 1652-1659
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer.Methods: Weconducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype.Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis.Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2.Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.
|
|
| 2. |
- Yang, Meng, et al.
(författare)
-
Prediagnosis leukocyte telomere length and risk of ovarian cancer
- 2016
-
Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 22
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Ovarian cancer is characterized by substantial genomic instability. Telomeres, which protect the physical integrity of chromosomes, are shortened by each cell division, and evidence supports that longer telomeres may reduce genomic instability. While retrospective studies generally support an inverse association of telomere length and ovarian cancer risk, the measures of telomere length after diagnosis may be influenced by treatment. Therefore, we examined the relationship between leukocyte telomere length (LTL) assessed prior to diagnosis and risk of ovarian cancer in three prospective studies. Methods: We used buffy coat samples collected from healthy participants in the Nurses' Health Study (NHS), NHSII, and the Northern Sweden Health and Disease Study (NSHDS). Women who later developed ovarian cancer were matched to one or two controls on age, menopausal status, and date of blood collection. LTL was assessed using quantitative PCR-based assays in 5 batches with coefficients of variation of 10-15%. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, based on study-specific quartiles in controls, for each study separately. We used fixed-effects models for meta-analysis. Multivariate models adjusted for oral contraceptive use, tubal ligation, family history of ovarian cancer, parity, smoking status, and body mass index. Results: In total, there were 487 cases and 810 controls across the three studies. The mean age at blood collection ranged from 45 (NHSII) to 57 (NHS) years. In unadjusted and multivariate models, we observed a suggestion of an inverse association between LTL and ovarian cancer risk in each study, although none of the trend tests were statistically significant. In a meta-analysis of the multivariate adjusted models, women in the longest versus shortest quartile of LTL had a non-significant 26% lower risk of ovarian cancer (OR=0.74; 95%CI=0.49-1.12; p-trend=0.33). Conclusion: In this first prospective study of telomere length and ovarian cancer risk, we observed that longer leukocyte telomere length was suggestively associated with lower ovarian cancer risk. Given that serous tumors are more likely to exhibit genomic instability, we are currently evaluating the association for this subtype as well as conducting pooled analyses with common quartile cut points across studies.
|
|
| 3. |
- Yang, Meng, et al.
(författare)
-
Prediagnosis Leukocyte Telomere Length and Risk of Ovarian Cancer
- 2017
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:3, s. 339-345
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The associations between telomere length and cancer risk are equivocal, and none have examined the association between prediagnosis leukocyte telomere length (LTL) and the risk of developing ovarian cancer. Methods: We prospectively measured LTL collected from 442 ovarian cancer cases and 727 controls in the Nurses' Health Studies and the Northern Sweden Health and Disease Study. Cases were matched to one or two controls on age, menopausal status, and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: LTL was measured a median of 9.5 years before ovarian cancer diagnosis among cases. We observed a decreased risk of ovarian cancer with longer LTL. In multivariable models, women in the top quartile of LTL had an OR for ovarian cancer of 0.67 (95% CI, 0.46-0.97) compared with those in the bottom quartile. Inverse associations were stronger for nonserous cases (ORquartile (4 vs. quartile 1 of LTL) = 0.55, 95% CI, 0.33-0.94) and rapidly fatal cases (i.e., cases who died within 3 years of diagnosis; ORquartile 4 vs. quartile 1 of LTL = 0.55, 95% CI, 0.32-0.95). Conclusions: Our prospective findings suggest that longer circulating LTL may be associated with a lower ovarian cancer risk, especially for nonserous and rapidly fatal cases. The evaluation of LTL in relation to ovarian cancer risk by tumor subtypes is warranted in larger prospective studies. Impact: Prediagnosis LTL may reflect an early event in the ovarian cancer development and could serve as a biomarker to predict future risk.
|
|
| 4. |
- Fortner, Renée T., et al.
(författare)
-
Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium
- 2019
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
|
|
| 5. |
- Jung, Seungyoun, et al.
(författare)
-
Anti‐Müllerian hormone and risk of ovarian cancer in nine cohorts
- 2018
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:2, s. 262-270
-
Tidskriftsartikel (refereegranskat)abstract
- Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (Ptrend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
|
|
| 6. |
- Sasamoto, Naoko, et al.
(författare)
-
Development and validation of circulating CA125 prediction models in postmenopausal women
- 2019
-
Ingår i: Journal of Ovarian Research. - : BioMed Central (BMC). - 1757-2215. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.Methods: We developed and validated linear and dichotomous (>= 35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
|
|
| 7. |
- Sasamoto, Naoko, et al.
(författare)
-
Predicting Circulating CA125 Levels among Healthy Premenopausal Women
- 2019
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1076-1085
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
|
|
| 8. |
- Schock, Helena, 1984-
(författare)
-
Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies.Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy.Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02], ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07], ptrend=0.07). The inverse association between IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96], ptrend=0.03). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology.The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements.Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.
|
|
| 9. |
- Trudel-Fitzgerald, Claudia, et al.
(författare)
-
The Association of Work Characteristics With Ovarian Cancer Risk and Mortality
- 2017
-
Ingår i: Psychosomatic Medicine. - : Lippincott Williams & Wilkins. - 0033-3174 .- 1534-7796. ; 79:9, s. 1059-1067
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Ovarian cancer (OvCA) is a leading cause of cancer death for women. Depression and social isolation have been associated with a higher OvCA risk and poorer survival, but other forms of chronic psychosocial stress, including work-related characteristics, remain understudied. Methods: Women from three prospective cohorts (Nurses' Health Study: n = 31,754; Nurses' Health Study II: n = 74,260; Northern Sweden Health and Disease Study: n(nested case-control study) = 196) completed a job questionnaire, assessing demand and control at work, social support provided by coworkers and supervisor, and job security. Multivariate Cox and conditional logistic regression models estimated hazard ratios (Nurses' Health Study/Nurses' Health Study II) and odd ratios (Northern Sweden Health and Disease Study) of OvCA risk and mortality among cases. Random coefficient models were used for meta-analyses. Results: There were 396 OvCA cases and 186 deaths during follow-up. Overall, job strain, strain chronicity, social support, and job security were not significantly associated with OvCA risk (e.g., pooled relative risk [RR](high demand/low control) = 1.06, confidence interval [CI] = 0.72-1.55) or mortality (e.g., pooled RRhigh demand/low control = 1.08, CI = 0.64-1.82). When considered individually, compared with low levels, only moderate levels of demand were associated with a reduced OvCA risk (pooled RR = 0.66, CI = 0.49-0.90). Social support provided by the coworker or the supervisor did not moderate the association of job strain with either OvCA risk or overall mortality. Conclusions: We did not observe clear associations between work characteristics and OvCA incidence or mortality, but further research with diverse populations is warranted.
|
|
| 10. |
|
|
