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OBJECTIVE: To evaluate if exercise and sitting time during chemotherapy were associated with chemotherapy side-effects, completion of planned chemotherapy and survival. METHODS: We used data from the Ovarian cancer Prognosis And Lifestyle (OPAL) Study, a national prospective cohort of adults with newly-diagnosed epithelial ovarian cancer. At 3-monthly questionnaires we asked about exercise and sitting time in the past week, and treatment-related side-effects. Details about treatment, toxicities, progression and death were abstracted from medical records. We used linear, logistic and Cox regression, respectively, to assess associations between both exercise and sitting time, and chemotherapy side-effects and completion (≥85% relative dose intensity) and survival. RESULTS: 503 eligible participants were included in one or more analyses. Patients participating in higher-intensity exercise (≥30 min of moderate-vigorous exercise/week; 24%) reported significantly better Functional Assessment of Chronic Illness/Cancer Therapy (FACIT)-Fatigue (32.2 vs. 26.7) and FACT-Trial Outcome Index (69.4 vs. 61.7) scores, and were less likely to have clinician-reported moderate-severe neurotoxicity (odds ratio [OR]:0.50; 95% confidence interval [95%CI]:0.29-0.88), than minimal exercisers (<30 min moderate-vigorous exercise/week & <120 min walking/week; 52%). Participating in higher-intensity exercise was also possibly associated with greater chemotherapy completion (OR:1.70; 95%CI:0.90-3.20), particularly for paclitaxel. Sitting time was not associated with chemotherapy completion. For patients with advanced disease who underwent cytoreduction and received first-line carboplatin and paclitaxel, there was a suggestion higher-intensity exercise during chemotherapy may improve survival (HR:0.68; 95%CI:0.47-1.01). CONCLUSIONS: Patients with ovarian cancer who carry out moderate-vigorous exercise during chemotherapy have fewer side-effects and potentially better completion of planned chemotherapy and overall survival.
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BACKGROUND: Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users. METHODS: Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004-12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients. RESULTS: Of the 313â383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up. CONCLUSIONS: Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.
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Carcinoma Epitelial do Ovário , Difosfonatos , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/epidemiologia , Idoso , Pessoa de Meia-Idade , Austrália/epidemiologia , Difosfonatos/uso terapêutico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Nitrogênio , Fatores de RiscoRESUMO
BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain. METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival. CONCLUSION: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes.
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OBJECTIVES: There is an active debate regarding whether metformin use improves survival in people with ovarian cancer. We examined this issue using methods designed to avoid immortal time bias-as bias that occurs when participants in a study cannot experience the outcome for a certain portion of the study time. METHODS: We used time-dependent analyses to study the association between metformin use for all 4,951 patients diagnosed with ovarian cancer in 1997 through 2018 in the province of British Columbia, Canada. Cox proportional hazards models were run to estimate the association between metformin and survival in the full cohort of ovarian cancer patients and among a cohort restricted to patients with diabetes. RESULTS: Metformin use was associated with a 17 % better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.83 (95 %CI 0.67, 1.02)), and a 16 % better ovarian cancer survival for serous cancers patient's cohort (aHR = 0.84 (95 %CI 0.66, 1.07)), although both were not significant. However, a statistically significant protective effect was observed when restricting to the diabetic cohort (aHR = 0.71 (95 %CI 0.54-0.91)), which was also seen among serous cancers (aHR = 0.73 (95 %CI 0.54-0.98)). CONCLUSION: Metformin use was associated with improved ovarian cancer survival. The lack of statistical significance in the full cohort may reflect that diabetes is associated with reduced cancer survival, and thus diabetes itself may offset the benefit of metformin when examining the full cohort. Future research should examine metformin use among non-diabetic ovarian cancer patients.
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Hipoglicemiantes , Metformina , Neoplasias Ovarianas , Humanos , Feminino , Metformina/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Colúmbia Britânica/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Hipoglicemiantes/uso terapêutico , Modelos de Riscos Proporcionais , AdultoRESUMO
BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.
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BACKGROUND & AIMS: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. METHODS: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. RESULTS: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. CONCLUSION: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. CLINICAL TRIALS REGISTRY: (ACTRN12613000743763).
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População Australasiana , Disfunção Erétil , Idoso , Humanos , Masculino , Austrália/epidemiologia , Calcifediol , Suplementos Nutricionais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/epidemiologia , Vitamina D , Vitaminas/uso terapêutico , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
Globally, ovarian cancer is the eighth most common cancer in women, accounting for an estimated 3.7% of cases and 4.7% of cancer deaths in 2020. Until the early 2000s, age-standardized incidence was highest in northern Europe and North America, but this trend has changed; incidence is now declining in these regions and increasing in parts of eastern Europe and Asia. Ovarian cancer is a very heterogeneous disease and, even among the most common type, namely epithelial ovarian cancer, five major clinically and genetically distinct histotypes exist. Most high-grade serous ovarian carcinomas are now recognized to originate in the fimbrial ends of the fallopian tube. This knowledge has led to more cancers being coded as fallopian tube in origin, which probably explains some of the apparent declines in ovarian cancer incidence, particularly in high-income countries; however, it also suggests that opportunistic salpingectomy offers an important opportunity for prevention. The five histotypes share several reproductive and hormonal risk factors, although differences also exist. In this Review, we summarize the epidemiology of this complex disease, comparing the different histotypes, and consider the potential for prevention. We also discuss how changes in the prevalence of risk and protective factors might have contributed to the observed changes in incidence and what this might mean for incidence in the future.
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Carcinoma Epitelial do Ovário , Saúde Global , Neoplasias Ovarianas , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Feminino , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Incidência , Saúde Global/estatística & dados numéricos , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/patologia , Fatores de Risco , PrevalênciaRESUMO
BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.
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Neoplasias do Endométrio , Hipertensão , Humanos , Feminino , Neoplasias do Endométrio/epidemiologia , Fatores de Risco , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Adulto , IncidênciaRESUMO
Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
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OBJECTIVE: To test the hypothesis that mismatch repair (MMR) status (as an accurate surrogate marker for microsatellite stability) modifies the effect of surgical approach on oncological outcome for apparent early-stage endometrial cancer. METHODS: Observational data from a large prospective population study on endometrial cancer were analyzed using target trial methodology and doubly robust methods, including propensity score matching and adjusted regression analyses. Laparoscopy was compared with laparotomy, stratified by MMR status on outcomes of recurrence and site, and recurrence-free, overall, and disease-specific survival. RESULTS: After matching, there were 400 patients for analysis, with 200 in each treatment group. The mean age was 62 years and mean body mass index was 32 kg/m2. Most patients had early-stage disease (stage I n=362 (90%)) and endometrioid histology (n=363 (91%)). Adjuvant pelvic radiation was administered to 11%, adjuvant vaginal brachytherapy to 13% and adjuvant chemotherapy to 5% of patients. Five-year recurrence-free survival did not differ significantly between modes of surgery across the cohort (p=0.7) or within MMR strata (MMR-proficient p=0.9, MMR-deficient p=0.6). Similarly, there was no significant difference in overall or disease-specific survival by mode of surgery across the cohort or within MMR strata. There was no significant difference in the HR for recurrence for those treated with laparoscopy stratified by MMR status (MMR-proficient HR=0.99 (95% CI 0.28 to 3.58); MMR-deficient HR=0.83 (95% CI 0.24 to 2.87)), even when restricted to endometrioid subtype. CONCLUSION: In this study, there was no evidence of a difference in survival outcomes according to mode of surgery and MMR status.
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Neoplasias Encefálicas , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio , Síndromes Neoplásicas Hereditárias , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estadiamento de Neoplasias , Endométrio/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/cirurgiaRESUMO
BACKGROUND: Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers. METHODS: We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable. RESULTS: IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status. CONCLUSIONS: Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers. IMPACT: Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.
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Proteína BRCA1 , Proteína BRCA2 , Neoplasias Ovarianas , Feminino , Humanos , Gravidez , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Fatores de Risco , Fumar/efeitos adversosRESUMO
OBJECTIVE: We aimed to explore the supportive care needs of ovarian cancer patients and their caregivers before and after the first cancer recurrence, the top unmet needs after recurrence, and the relationship between patient and caregiver needs at recurrence. METHODS: Participants were 288 patients and 140 caregivers from the Australian Ovarian Cancer Study-Quality of Life (AOCS-QoL) cohort. They completed Supportive Care Needs Surveys (patients: SCNS-SF34, caregivers: SCNS-P&C44) every three-to-six months for up to two years. Linear mixed models tracked changes in needs over time. We calculated the percentage reporting moderate-to-high needs after recurrence. LASSO regression analysed patient-caregiver need relationships. RESULTS: Both patients' and caregivers' psychological, health system/service and information needs increased with recurrence along with patients' support and physical needs. These remained stable at nine months after recurrence. Dominant patient needs post-recurrence included 'fear of recurrence' (38%) and 'concerns about the worries of those close' (34%), while caregivers expressed 'concerns about recurrence' (41%) and 'recovery of the patient not turning out as expected' (31%). Among dyads, when patients had 'fears about the cancer spreading' this was associated with caregivers having a need for help with 'reducing stress in the patients' life'; when caregivers had concerns about 'recurrence' this was associated with patients needing help with 'uncertainty about the future' and 'information about things they can do to help themselves'. CONCLUSIONS: Recurrent ovarian cancer intensifies disease-related fears and concerns for patients and loved ones. Addressing dyadic concerns through supportive care interventions may enhance cohesion during the challenging journey of recurrent disease.
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Cuidadores , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Apoio Social , Humanos , Feminino , Cuidadores/psicologia , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/psicologia , Idoso , Qualidade de Vida , Adulto , Austrália , Avaliação das Necessidades , Necessidades e Demandas de Serviços de SaúdeRESUMO
AIMS: To investigate anxiety and depression after primary treatment for ovarian cancer in relation to diet quality and intake. METHODS: In a cohort of women with ovarian cancer in Australia, levels of anxiety and depression (normal, subclinical, and clinical) were assessed using the Hospital Anxiety and Depression Scale at 9 months post-diagnosis. Dietary intake was assessed using a validated food frequency questionnaire at 12 months post-diagnosis and scored using the Healthy Eating Index 2015. Multinomial logistic regression and bivariate analyses were used to investigate relationships between levels of anxiety and depression and subsequent diet quality and intake of food groups. RESULTS: Of 595 women, anxiety and depression were identified among 128 (21%) and 80 (13%) women, respectively. Compared to women without anxiety or depression, women with subclinical anxiety (odds ratio = 0.49, 95% confidence interval: 0.25-0.98) and those with clinical depression (odds ratio = 0.25, 95% confidence interval: 0.07-0.93) were less likely to score in the highest quartile for diet quality. Separate adjustment for age, education, employment, disease stage, body mass index, and smoking status did not attenuate these associations. In bivariate analyses, women with subclinical anxiety were more likely to report higher intakes of sweet foods. Those with clinical depression were more likely to report lower intakes of orange vegetables and wholegrains, higher intakes of sweetened beverages, and not consume alcohol or soya foods. CONCLUSIONS: Anxiety or depression after primary treatment for ovarian cancer may be associated with poorer diet quality. Efforts to improve diet quality post-treatment should consider support for mental health.
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Ansiedade , Depressão , Dieta , Saúde Mental , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Austrália , Depressão/epidemiologia , Dieta Saudável , Idoso , Adulto , Estudos de Coortes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Estudos de Coortes , Austrália/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/diagnóstico , Fatores de Risco , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnósticoRESUMO
PURPOSE: Five-year relative survival for ovarian cancer remains below 50%. Strategies to improve outcomes are needed. Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations [measure of vitamin D status] at and before diagnosis have been associated with longer survival in cancer patients; however, data for ovarian cancer are limited. We aimed to determine if 25(OH)D concentrations during and after primary treatment were associated with ovarian cancer-specific survival. METHODS: We used data from a nationwide prospective cohort study of women with ovarian cancer. Among 886 participants treated with chemotherapy, 700 (79%) had a blood sample collected during (n = 591) and/or after (n = 458) primary treatment. These were tested for 25(OH)D. Clinical and survival data were abstracted from medical records. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 25(OH)D and ovarian cancer-specific survival. RESULTS: Mean 25(OH)D concentrations were lower during than after primary treatment (82 and 91 nmol/L, respectively); only 14% and 8% had concentrations below 50 nmol/L during and after primary treatment, respectively. There was no association between 25(OH)D and ovarian cancer-specific survival during five years of follow-up [HR 1.10 (95% CI: 0.76, 1.61) and 0.95 (0.54, 1.68) for the highest vs. lowest quintile during and after treatment, respectively]. CONCLUSIONS: We did not observe any association between serum 25(OH)D concentration and ovarian cancer-specific survival. Our results suggest that, in the absence of vitamin D deficiency, vitamin D supplementation to improve ovarian cancer survival is not warranted.
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Neoplasias Ovarianas , Deficiência de Vitamina D , Humanos , Feminino , Estudos Prospectivos , Vitamina D , Deficiência de Vitamina D/epidemiologia , Vitaminas/uso terapêuticoRESUMO
Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.
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Hipotireoidismo , Tiroxina , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Austrália/epidemiologia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Preparações Farmacêuticas , Suplementos Nutricionais/análise , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Hipotireoidismo/prevenção & controle , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.
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Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.
Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Fatores de Risco , Medição de Risco , Estudos de Casos e ControlesRESUMO
BACKGROUND: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC. METHODS: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves. RESULTS: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage. CONCLUSION: This multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.