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| 2. |
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| 3. |
- Allen, Naomi E, et al.
(författare)
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Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2008
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 15:2, s. 485-497
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.
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| 4. |
- Campa, Daniele, et al.
(författare)
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The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk
- 2010
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 10, s. 563-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC).METHODS: we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk.RESULTS AND CONCLUSIONS: In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
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| 5. |
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| 6. |
- Cust, Anne E., et al.
(författare)
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Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 14:3, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
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| 7. |
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| 8. |
- Dossus, Laure, et al.
(författare)
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Obesity, inflammatory markers, and endometrial cancer risk : a prospective case-control study
- 2010
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:4, s. 1007-1019
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Tidskriftsartikel (refereegranskat)abstract
- Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
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| 9. |
- Dossus, Laure, et al.
(författare)
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Reproductive risk factors and endometrial cancer : the European prospective investigation into cancer and nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:2, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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| 10. |
- Dossus, Laure, et al.
(författare)
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Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
- 2011
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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| 11. |
- Fedirko, Veronika, et al.
(författare)
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Alcohol drinking and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Annals of Epidemiology. - : Elsevier BV. - 1047-2797 .- 1873-2585. ; 23:2, s. 93-98
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Alcohol intake may adversely affect the concentrations of endogenous sex hormones, and thus increase the risk of endometrial cancer. However, epidemiologic studies have provided conflicting results. Therefore, we investigated the association between alcohol intake and endometrial cancer risk a large, multicenter, prospective study. Methods: From 1992 through 2010, 301,051 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed for incident endometrial cancer (n = 1382). Baseline alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. Results: The multivariable HRs (and 95% CIs) compared with light drinkers (0.1-6 g/d) were 1.03(0.88-1.20) for 0 g of alcohol per day at baseline, 1.01 (0.86-1.17) for 6.1-12 g/d, 1.03 (0.87-1.22) for 12.1-24 g/d, 1.07(0.87-1.38) for 241-36 g/d, and 0.85(0.61-1.18) for more than 36 g/d (p(trend) = 0.77). No association was observed among former drinkers (OR, 1.28; 95% CI, 0.98-1.68 compared with light drinkers). Null associations were also found between alcohol consumption at age 20 years, lifetime pattern of alcohol drinking, and baseline alcohol intake from specific alcoholic beverages and endometrial cancer risk. Conclusions: Our findings suggest no association between alcohol intake and endometrial cancer risk.
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| 12. |
- Fortner, Renee T., et al.
(författare)
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Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:6, s. 1317-1323
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimina-tion. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigat-ed for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selec-tion process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were select-ed into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including eti-ologic markers on independent pathways and genetic markers may further improve discrimination.
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| 13. |
- Fortner, Renée T., et al.
(författare)
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Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels : Results from the EPIC cohort
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:7, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; p(het)=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. What's new? Although CA125, a mucin produced in epithelial cells, is a known marker for ovarian cancer, complementary biomarkers are necessary for reliable early cancer detection. Here, the authors examined autoantibodies against CA125 as potential pre-diagnosis markers. Although anti-CA125 levels did not discriminate between ovarian cases and controls, discrimination of CA125 differed by levels of its antibody, with the highest discrimination among women with the highest antibody levels. The authors propose that CA125 and anti-CA125 may act synergistically for ovarian cancer early detection.
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| 14. |
- Fortner, Renee T., et al.
(författare)
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Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:5, s. 1196-1208
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Tidskriftsartikel (refereegranskat)abstract
- Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (p(het)=0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; p(het)=0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes. What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated. However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood. Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway. The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
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| 15. |
- Kaaks, Rudolf, et al.
(författare)
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Tumor-associated autoantibodies as early detection markers for ovarian cancer? : A prospective evaluation
- 2018
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 143:3, s. 515-526
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Tidskriftsartikel (refereegranskat)abstract
- Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times 6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. What's new? Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer-specific as expected.
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| 16. |
- Lahmann, Petra H., et al.
(författare)
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Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:10, s. 2404-2415
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Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (as), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m(2), obesity (BMI >= 30 kg/m(2)) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% Cl = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% Cl = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% Cl = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% Cl = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.
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| 17. |
- Merritt, Melissa A., et al.
(författare)
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 38:5, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR = 1.22, 95% CI = 1.02-1.48, P-trend = 0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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| 18. |
- Mukama, Trasias, et al.
(författare)
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Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 126, s. 1301-1309
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Tidskriftsartikel (refereegranskat)abstract
- Background: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.Results: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.Conclusion: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.
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| 19. |
- Obon-Santacana, Mireia, et al.
(författare)
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Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer : A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 25:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent.Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk.Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed.Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC.Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk.
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| 20. |
- Ose, Jennifer, et al.
(författare)
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Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort.
- 2015
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 24:6, s. 951-961
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Terry, Kathryn L., et al.
(författare)
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A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort
- 2016
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 22:18, s. 4664-4675
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate earlydetection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases.
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| 25. |
- Yammine, Sahar, et al.
(författare)
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Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:9, s. 1739-1749
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis.Results: Apositive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintile(Q5-Q1) = 1.29; 95% confidence interval (CI) = 1.03-1.62; P-trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P-trend = 0.03) and n-3 alpha-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P-trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile(T3-T1) = 1.39; 95% CI = 0.99-1.94; P-trend = 0.06) anda-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P-trend = 0.06).Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and alpha-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.
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