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1.
Epidemiology ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32028322

RESUMO

BACKGROUND: Menopausal estrogen-alone therapy is a risk factor for endometrial and ovarian cancers. When a progestin is included with the estrogen daily (continuous estrogen-progestin combined therapy), there is no increased risk of endometrial cancer. However, the effect of continuous estrogen-progestin combined therapy on risk of ovarian cancer is less clear. METHODS: We pooled primary data from five population-based case-control studies in the Ovarian Cancer Association Consortium, including 1,509 postmenopausal ovarian cancer cases and 2,295 postmenopausal controls. Information on previous menopausal hormonal therapy use, as well as ovarian cancer risk factors, was collected using in-person interviews. Logistic regression was used to assess the association between use of continuous estrogen-progestin combined therapy and risk of ovarian cancer by duration and recency of use and disease histotype. RESULTS: Ever postmenopausal use of continuous estrogen-progestin combined therapy was not associated with increased risk of ovarian cancer overall (OR=0.85, 95% CI 0.72-1.0). A decreased risk was observed for mucinous ovarian cancer (OR=0.40, 95% CI 0.18-0.91). The other main ovarian cancer histotypes did not show an association (endometrioid: OR=0.86, 95% CI 0.57-1.3, clear cell: OR=0.68, 95% CI 0.40-1.2, serous: OR=0.98, 95% CI 0.80-1.2). CONCLUSIONS: Given that estrogen-alone therapy has been shown to be associated with increased risk of ovarian cancer, these findings are consistent with the hypothesis that adding a progestin each day ameliorates the carcinogenic effects of estrogen on the cells of origin for all histotypes of ovarian cancer.

2.
Psychoneuroendocrinology ; 112: 104515, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784054

RESUMO

A history of child abuse (CA) is associated with morbidity and mortality in adulthood, and one proposed mechanism is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we evaluated whether a history of physical and sexual CA was associated with daily rhythms of HPA hormones (cortisol and dehydroepiandrosterone (DHEA)) among postmenopausal women (mean age: 60.6 years). In 2013, 233 participants from the Nurses' Health Study II provided up to 5-timed saliva samples over the course of a day: immediately upon awakening, 45 min, 4 h, and 10 h after waking, and prior to going to sleep. Among these 233 participants, 217 provided ≥4 timed saliva samples. Assessment of physical and sexual CA history occurred in 2001 using the Revised Conflict Tactics Scale. Cumulative CA history was derived by combining reports of physical and sexual abuse prior to age 18. Piecewise linear mixed models compared diurnal rhythms of cortisol and DHEA between participants with none-to-moderate CA (n = 104, reference group) versus high-to-severe CA (n = 113). Models adjusted for characteristics at each saliva collection, health status, sleep quality, medications, and hormone use. Compared to those with none-to-moderate CA, women with high-to-severe CA had different diurnal rhythms in the early and evening hours, including blunted (less steep) early declines in DHEA (% difference (%D) = 10.7, 95 % Confidence Interval (CI) 4.3, 17.5), and steeper late declines in both cortisol and DHEA (cortisol %D = -2.5, 95 % CI -4.8, -0.1, and DHEA %D= -3.9, 95 % CI -6.0, -1.8). In conclusion, high-to-severe abuse history prior to age 18 was more strongly associated with differences in DHEA rather than cortisol, suggesting that early life abuse may be related to dysregulation of stress-response mechanisms later in life.

3.
J Ovarian Res ; 12(1): 116, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771659

RESUMO

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.

4.
Int J Cancer ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693173

RESUMO

Little is known about the influence of prediagnosis and postdiagnosis smoking and smoking cessation on ovarian cancer survival. We investigated this relationship in two prospective cohort studies, the Nurses' Health Study (NHS) and NHSII. Analyses included 1,279 women with confirmed invasive, Stage I-III epithelial ovarian cancer. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ovarian cancer-specific mortality by smoking status, adjusting for age and year of diagnosis, tumor stage, histologic subtype, body mass index and nonsteroidal anti-inflammatory use (postdiagnosis models only). When examining prediagnosis smoking status (assessed a median of 12 months before diagnosis), risk of death was significantly increased for former smokers (HR = 1.19, 95% CI: 1.02-1.39), and suggestively for current smokers (HR = 1.21, 95% CI: 0.96-1.51) vs. never smokers. Longer smoking duration (≥20 years vs. never, HR = 1.23, 95% CI: 1.05-1.45) and higher pack-years (≥20 pack-years vs. never, HR = 1.28, 95% CI: 1.07-1.52) were also associated with worse outcome. With respect to postdiagnosis exposure, women who smoked ≥15 cigarettes per day after diagnosis (assessed a median of 11 months after diagnosis) had increased mortality compared to never smokers (HR = 2.34, 95% CI: 1.63-3.37). Those who continued smoking after diagnosis had 40% higher mortality (HR = 1.40, 95% CI: 1.05-1.87) compared to never smokers. Overall, our results suggest both prediagnosis and postdiagnosis smoking are associated with worse ovarian cancer outcomes.

5.
Cancer Epidemiol Biomarkers Prev ; 28(11): 1845-1852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387969

RESUMO

BACKGROUND: Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. METHODS: We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. RESULTS: There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). CONCLUSIONS: Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. IMPACT: Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

6.
Int J Epidemiol ; 48(3): 822-830, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211375

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

7.
Cancer Epidemiol Biomarkers Prev ; 28(6): 1076-1085, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30948451

RESUMO

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.
Cancer Med ; 8(5): 2503-2513, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31001917

RESUMO

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

9.
Br J Cancer ; 120(8): 855-860, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30894687

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) are associated with pelvic inflammatory disease and tubal pathologies. Given the tubal origin of a proportion of ovarian cancers, STIs may be relevant in their aetiology. METHODS: Antibodies indicating past infection with Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus type 2, and against human papillomavirus oncogenes (L1 and E6+E7 oncoproteins of types 16, 18, 45) were measured in prediagnosis plasma samples in a nested case-control study in the Nurses' Health Studies (n = 337 cases 1:1 matched to controls). Logistic regression was used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals [CIs] comparing women seropositive vs. seronegative among all cases (invasive and borderline), invasive (n = 257), and invasive serous ovarian cancers; n = 170), and borderline ovarian tumours (n = 80). RESULTS: C. trachomatis seropositivity was associated with higher risk of ovarian cancer overall (RR = 2.07 [1.25-3.43]); results were similar for invasive, invasive serous, and borderline tumours. We observed no associations for the other STIs. Relative to women seronegative to all infections, strongest associations were observed for seropositivity to C. trachomatis plus another STI (2.74 [1.20-6.27]; C. trachomatis alone, 1.88 [1.03-3.42]; all cases); however, the RRs were not significantly different. CONCLUSIONS: C. trachomatis infection may increase ovarian cancer risk; additional studies are required.

10.
Cancer Causes Control ; 30(5): 537-547, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30905014

RESUMO

PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR = 1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR = 1.28; 95% CI 1.08-1.52, and HR = 1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Neoplasias Ovarianas/epidemiologia , Comportamento Sedentário , Fumar/epidemiologia , Feminino , Humanos , Atividade Motora , Obesidade/complicações , Neoplasias Ovarianas/mortalidade , Sobrepeso/complicações , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/efeitos adversos , Ganho de Peso
11.
Am J Perinatol ; 36(14): 1485-1491, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30695793

RESUMO

OBJECTIVE: To evaluate whether cervical dilation predicts the timing and likelihood of spontaneous labor at term. STUDY DESIGN: This was a retrospective cohort of nulliparous women with singleton pregnancies who delivered at term from 2013 to 2015. Outpatient cervical examinations performed after 37 weeks and prior to labor onset were collected. Survival analysis was used to analyze time to spontaneous labor with cervical dilation as the primary predictor, modeled as continuous and categorical variables (<1 cm, 1 cm, >1 cm). RESULTS: Our cohort included 726 women; 407 (56%) spontaneously labored, 263 (36%) were induced, and 56 (8%) had an unlabored cesarean delivery. Women with >1-cm dilation were three times more likely to spontaneously labor (adjusted hazard ratio [aHR]: 3.1; 95% confidence interval [CI]: 2.4-4) than those with <1-cm dilation. At 39 weeks, 60% of women with >1-cm dilation went into spontaneous labor as compared with only 28% of those with <1-cm dilation (aHR: 2.9; 95% CI: 2-4.4). CONCLUSION: In our cohort of nulliparous women at term, those with cervical dilation > 1 cm were significantly more likely to go into labor in the following week. This information can aid in counseling about elective induction of labor.

12.
Int J Cancer ; 144(9): 2192-2205, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30499236

RESUMO

As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case-control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10-4 ). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46-0.60) compared to 0.71 (95%CI = 0.66-0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1-5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene-environment analysis in ovarian cancer.


Assuntos
Exposição Ambiental/efeitos adversos , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/genética , Estudos de Casos e Controles , Anticoncepcionais Orais Hormonais , Meio Ambiente , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Risco
13.
Int J Cancer ; 144(5): 991-1000, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30006925

RESUMO

Statins are widely used to lower blood cholesterol and reduce risk for cardiovascular diseases, but attention has recently focused on a role in cancer prevention or therapy. Here we present data from a large case-control study addressing whether statin use can lower the risk for epithelial ovarian cancer (EOC). Between 1992 and 2008, data including medications used for at least 6 months were collected from 2,040 cases with EOC and 2,100 frequency-matched controls without the disease who participated in the New England Case Control study. We used unconditional logistic regression controlling for matching factors and potential confounders to examine the association between statin use and the risk for EOC. Overall, women who used statins had 32% lower risk of ovarian cancer compared to non-users (Odds ratio (OR) 0.68, 95% Confidence Interval (CI): 0.54-0.85), adjusting for the matching factors and other covariates. The reduced risk was most apparent in women taking a lipophilic statin who began use after age 49, and who had used them 2-4.9 years. Statin use was associated with lower risks for both serous and non-serous histologic subtypes with the strongest effect seen for mucinous and mixed epithelial subtypes. The association became apparent about a decade after the introduction of statins and did not appear to be confounded by indications for use of statins or medications used concomitantly. In this case-control study, statins were found to lower the risk for both serous and non-serous EOC and especially mucinous EOC.


Assuntos
Carcinoma Epitelial do Ovário/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Ovarianas/induzido quimicamente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , New England , Razão de Chances , Fatores de Risco
14.
Stress ; 22(1): 60-69, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30585520

RESUMO

Stress is an important and modifiable determinant of health, and its association with hair cortisol concentrations (HCC) during pregnancy remains unclear. We selected a random sample of 97 participants from a cohort of pregnant participants attending prenatal clinics in Lima, Peru. Each provided a hair sample at enrollment (mean gestational age = 13.1 weeks) and again at full-term delivery. Hair samples were segmented to reflect HCC in preconception and each trimester. At enrollment, measures of stress included: difficulty accessing basic goods, educational attainment, exposure to violence, fair or poor general health, perceived stress, and symptoms of depression, general anxiety, and post-traumatic stress disorder. Linear mixed models evaluated the association between each stress measure and absolute and relative changes in HCC. Pearson correlation coefficients (r) assessed correlations between HCC and continuous stress scores. Educational attainment of ≤12 years was associated with higher HCC in preconception and the 1st trimester, and general anxiety with lower preconception HCC. When modeling HCC patterns across the 4 hair segments, an educational attainment of ≤12 years was associated with higher HCC, high perceived stress with lower HCC, and general anxiety with steeper increases in HCC (group by time p value = .02). Only preconception HCC and GAD scores correlated (r = -0.22, p = .04). We observed few associations between stress and HCC. However, those that were seen were generally restricted to the preconception and 1st trimester. Further investigations into the association between stress and changes in HCC across pregnancy are warranted, and should include the preconception where possible.


Assuntos
Cabelo/metabolismo , Hidrocortisona/metabolismo , Gravidez/metabolismo , Estresse Psicológico/metabolismo , Adulto , Ansiedade/etiologia , Ansiedade/metabolismo , Estudos de Coortes , Depressão/etiologia , Depressão/metabolismo , Transtorno Depressivo/etiologia , Transtorno Depressivo/metabolismo , Feminino , Idade Gestacional , Cabelo/química , Humanos , Hidrocortisona/análise , Neoplasias Hepáticas , Masculino , Gravidez/psicologia
15.
Cancer Epidemiol Biomarkers Prev ; 27(12): 1509-1517, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30377203

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use may affect ovarian cancer risk via prostaglandin synthesis and tumor-associated macrophage (TAM) infiltration. We evaluated if associations between aspirin or non-aspirin NSAID use and ovarian cancer risk differed by tumor expression of prostaglandin-related (COX1, COX2) and TAM-related (CD68, CD163) markers. METHODS: We evaluated cases and matched controls from the Nurses' Health Study (NHS), NHSII, and New England Case-Control Study (NECC). Cases with IHC data on COX1 and COX2 (n = 532) or CD68 and CD163 (n = 530) were included. We used polytomous logistic regression, adjusted for ovarian cancer risk factors, to estimate OR for NSAID use and ovarian cancer risk by marker level. RESULTS: Recent aspirin use had a nonsignificant inverse association and recent non-aspirin NSAID use had no association with ovarian cancer risk. NSAID use was not differentially associated with ovarian cancer by COX1 or COX2 expression. However, recent aspirin use was associated with lower ovarian cancer risk for high [OR 0.54; 95% confidence interval (CI), 0.37-0.78], but not low (OR 1.50; 95% CI, 0.97-2.31), CD163 density (P heterogeneity < 0.001). Similar results were observed for aspirin duration and tablets and for recent non-aspirin NSAID use. Results were not clearly different by macrophage density defined by the less specific macrophage marker, CD68. CONCLUSIONS: NSAID use was inversely associated with risk of ovarian cancer with high density CD163, a marker for M2-type, immunosuppressive macrophages. However, the relationship did not differ by prostaglandin synthesis markers. IMPACT: Future research should explore prostaglandin-independent mechanisms for the association between NSAID use and ovarian cancer risk, including immune mechanisms.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Macrófagos/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/farmacologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Fatores de Risco
16.
JAMA Oncol ; 4(12): 1675-1682, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30286239

RESUMO

Importance: Ovarian cancer is a highly fatal malignant neoplasm with few modifiable risk factors. Case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin. Objective: To evaluate whether regular aspirin or nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use and patterns of use are associated with lower ovarian cancer risk. Design, Setting, and Participants: This cohort study analyzed NSAID use and ovarian cancer diagnosis data from 2 prospective cohorts, 93 664 women in the Nurses' Health Study (NHS), who were followed up from 1980 to 2014, and 111 834 in the Nurses' Health Study II (NHSII), who were followed up from 1989 to 2015. Follow-up was completed on June 30, 2014, for the NHS and June 30, 2015, for NHSII. Data were analyzed from June 13, 2016, to September 18, 2017. Exposures: For each analgesic type (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen), timing, duration, frequency, and number of tablets used were evaluated; exposure information was updated every 2 to 4 years. Main Outcomes and Measures: Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of aspirin, nonaspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were 2-sided, with a significance level of .05. Results: In the NHS, the mean (SD) age at baseline (1980) was 45.9 (7.2) years, and 93% of participants identified as non-Hispanic white. In the NHSII, the mean age at baseline (1989) was 34.2 (4.7) years, and 92% identified as non-Hispanic white. Among the 205 498 women in both cohorts, there were 1054 cases of incident epithelial ovarian cancer. Significant associations between aspirin and ovarian cancer risk were not observed when current vs nonuse of any aspirin was evaluated regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). However, when low-dose (≤100-mg) and standard-dose (325-mg) aspirin were evaluated separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96), but no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49) was observed. Current use of nonaspirin NSAIDs was positively associated with risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend) were observed. There were no clear associations for the use of acetaminophen. Conclusions and Relevance: These results appear to be consistent with case-control studies that show a reduced risk of ovarian cancer among regular users of low-dose aspirin. An increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs, was observed, although this finding requires confirmation.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carcinoma Epitelial do Ovário/epidemiologia , Neoplasias Ovarianas/epidemiologia , Adulto , Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/classificação , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/estatística & dados numéricos , Fatores de Risco
17.
Cancer Epidemiol Biomarkers Prev ; 27(12): 1483-1490, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30237250

RESUMO

BACKGROUND: Randomized trials using the biomarker cancer antigen (CA) 125, with or without pelvic ultrasound, have failed to show a clear benefit of general population screening for ovarian cancer. In part, this may be due to a lack of information about conditions, besides ovarian cancer, that can alter CA125 levels and affect specificity or sensitivity. We evaluated the association between common medical conditions and CA125 levels among women without ovarian cancer. METHODS: We used data and specimens from 2,004 women without ovarian cancer who participated in the New England Case Control study between 1992 and 2008. Participants completed in-person interviews and donated blood samples at enrollment. We measured CA125 using the CA125II assay and calculated the association between medical conditions and log-transformed CA125 using linear regression. RESULTS: The median age of participants was 53 years and 1,119 (56%) were postmenopausal. The average CA125 level was 14.5 units/mL for premenopausal and 11.7 for postmenopausal women. Among premenopausal women, CA125 was significantly lower for women with colon polyps (P = 0.06) and hysterectomy (P = 0.01) and significantly higher with endometriosis (P = 0.05). CA125 was also significantly higher in premenopausal women with coronary artery disease (CVD) (P < 0.01, n = 2 cases) but not among postmenopausal with CVD (n = 79). Furthermore, among postmenopausal women, CA125 was significantly lower for women with osteoporosis, hypercholesterolemia, and osteoarthritis (P = 0.03, 0.02, and 0.01 respectively) and higher for women with a history of inflammatory bowel disease (P = 0.04). CONCLUSIONS: Several chronic diseases are associated with CA125, which could influence the interpretation of CA125 in the context of ovarian cancer screening. IMPACT: Consideration of chronic medical conditions may be necessary to interpret CA125 values.


Assuntos
Antígeno Ca-125/sangue , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade
18.
Cancer Epidemiol Biomarkers Prev ; 27(7): 790-804, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29661801

RESUMO

Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined.Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression.Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both.Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types.Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC. Cancer Epidemiol Biomarkers Prev; 27(7); 790-804. ©2018 AACR.


Assuntos
Biomarcadores Tumorais/genética , Antígeno Ca-125/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Fatores de Risco
19.
Stress ; 21(4): 355-365, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29614892

RESUMO

Distal hair segments collected at delivery may allow for the assessment of maternal cortisol secretion in early pregnancy, an important time window for fetal development. Therefore, an investigation of the validity of distal hair cortisol concentrations is warranted. We examined the concordance between proximal and distal hair cortisol concentrations (HCC), both representing the first trimester of pregnancy. The study population was comprised of a random sample of 97 women participating in the Pregnancy Outcomes Maternal and Infant Study, a prospective cohort study of pregnant women attending prenatal clinics in Lima, Peru. Each participant provided two hair samples: once at enrollment [mean gestational age (GA) = 13.1 weeks] and again at full-term delivery (mean GA = 39.0 weeks). Hair segments reflecting the first trimester were: 3 cm hair segments closest to the scalp on the first hair sample (proximal) and 6-9 cm from the scalp on the second hair sample (distal). HCC was determined using Luminescence Immunoassay. A subset (N = 28) had both hair segments additionally analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). HCC values were log-transformed (logHCC), and proximal-distal differences tested using paired sample t-tests. Concordance was evaluated within and across assay types. LogHCC, measured using immunoassay, in distal hair segments was lower compared to proximal hair segments (1.35 versus 1.64 respectively; p = .02). No difference was observed using LC-MS/MS (1.99 versus 1.83, respectively; p=.33). Proximal-distal concordance was low within assay (immunoassay: Pearson = 0.27 and κ = 0.10; LC-MS/MS: Pearson = 0.37 and κ = 0.07). High correlation was observed across assays for both distal (Pearson = 0.78, p < .001; κ = 0.64) and proximal segments (Pearson = 0.96, p < .001; κ = 0.75). In conclusion, distal first-trimester hair segments collected at delivery have lower absolute HCC compared to HCC in proximal first trimester hair segments collected in early pregnancy, and are poorly concordant with HCC in proximal segments. Findings may inform the design of future studies.


Assuntos
Cabelo/química , Hidrocortisona/análise , Parto/fisiologia , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Masculino , Gravidez , Estudos Prospectivos , Adulto Jovem
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