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1.
Sci Rep ; 11(1): 8524, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875740

RESUMO

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88-1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87-1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.

2.
Emerg Infect Dis ; 27(5): 1537-1540, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33900190

RESUMO

Temporal variation of respiratory syncytial virus (RSV) epidemics was recently reported to be determined by the dominant RSV subtype. However, when we repeated the analysis for 4 countries in the Northern and Southern Hemispheres, the dominant subtype did not seem to affect temporal variation of RSV epidemics.

3.
Crit Rev Oncol Hematol ; 160: 103288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33675908

RESUMO

We conducted a systematic review and meta-analysis of the association between somatic mutations of the TERT gene promoter and melanoma survival. Data from nineteen independent studies (>2,500 melanoma overall) were pooled using random effects meta-analysis models. TERT-mutated melanoma patients had a significantly worse overall survival (OS) (summary hazard ratio 1.43, 95 % confidence intervals (CI) 1.05-1.95) compared to wild-type ones. The association became stronger when combining risk estimates for overall and melanoma-specific survival (MSS) (1.52, 95 % CI 1.14-2.02), and when restricting the analysis to studies mostly based on invasive non-acral cutaneous melanomas (1.77, 95 % CI 1.00-3.15). Limited, yet suggestive evidence of a detrimental effect of TERT promoter mutations on melanoma prognosis emerged also for other survival measures (e.g. disease-free and distant metastasis-free survival). We found suggestive evidence of a detrimental effect of TERT mutations on melanoma patients' survival.


Assuntos
Melanoma , Neoplasias Cutâneas , Telomerase , Humanos , Melanoma/genética , Mutação , Prognóstico , Neoplasias Cutâneas/genética , Telomerase/genética
4.
Sci Rep ; 11(1): 7095, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782441

RESUMO

CSF shunting with adjustable valve is the treatment of idiopathic normal pressure hydrocephalus. The opening pressure valve setting is left to the neurosurgeon's experience. Aqueductal CSF stroke volume by phase-contrast magnetic resonance measures the CSF passing through the Sylvian aqueduct and it changes with intracranial hydrodynamics. We sought to identify a window of stroke volume differences associated with the best clinical outcome and lowest rate of complications. The records of 69 patients were reviewed. At every clinical check, stroke volume, opening pressure valve, clinical outcome, and CSF overdrainage were analyzed. The correlation between stroke volume differences and negative outcome was also analyzed. The median follow-up was 2.3 years (range 0.3-10.4 years). The odds of negative outcome between two consecutive checks significantly increased by 16% (95%CI 4-28%, p = 0.006). Taking the lowest risk group as reference, the odds ratio of negative outcome was 1.16 (95%CI 0.51-2.63, p = 0.726) for SV differences less than - 37.6 µL, while it was 1.96 (95%CI 0.97-3.98, p = 0.062) for stroke volume changes above + 23.1 µL. Maintaining stroke volume values within a definite range might help maximize clinical benefit and avoid the risk of CSF overdrainage.

5.
Crit Rev Oncol Hematol ; 159: 103242, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545356

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. EVIDENCE ACQUISITION: We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. EVIDENCE SYNTHESIS: A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. CONCLUSIONS: SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Preparações Farmacêuticas , Radiocirurgia , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Radiocirurgia/efeitos adversos
6.
Mol Carcinog ; 60(3): 167-171, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444485

RESUMO

Germline variants of the melanocortin-1-receptor (MC1R) gene are the most common genetic trait predisposing to cutaneous melanoma (CM). Here, we performed a literature review and meta-analysis of the association between MC1R gene variants and the frequency of somatic mutations of the BRAF, NRAS, and TERT genes in CM patients. We included studies published until January 2020 in MEDLINE, EMBASE, Ovid Medline, and two grey literature databases. Random effect models were used to pool study-specific estimates into summary odds ratio (SOR) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and assess the robustness of pooled estimates. Twelve studies published between 2006 and 2018 (encompassing 3566 CM, mostly on nonacral sites) were included. MC1R gene variants were not significantly associated with the frequency of somatic mutations of the BRAF and NRAS genes. Only three studies focused on somatic mutations of the TERT gene promoter, all of which reported moderate-to-strong positive associations with MC1R germline variants. MC1R gene variants appear to make only moderate changes, if any, to the risk of BRAF- or NRAS-mutant CM. The association with TERT promoter mutations is suggestive, yet it warrants confirmation as it is based on a still limited number of studies.


Assuntos
GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Receptor Tipo 1 de Melanocortina/genética , Neoplasias Cutâneas/genética , Telomerase/genética , Variação Genética , Mutação em Linhagem Germinativa , Humanos , Mutação
7.
Crit Rev Oncol Hematol ; 158: 103202, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387627

RESUMO

Vitamin D receptors polymorphisms are found to be associated with several cancers. Since their prevalence vary across ethnicities and ethnicity itself seems to influence the cancer risk, a comprehensive meta-analysis was performed to investigate the role of VDR Fok1, Bsm1, Taq1, Apa1, Cdx2 and cancer risk at specific organ sites. Odds ratios, calculated with random-effects models, summarized one-hundred-ninety-two independent studies for twenty-two cancer sites. Evidence was provided that Fok1, Bsm1, Cdx2, Apa1 and Taq1 are linked to cancer susceptibility for colorectal, lung, ovarian, skin, multiple myeloma and brain cancer. Stratifying by ethnicity, some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations. In summary, ethnicity may be a modifier of cancer risk, in particular for hormone dependent cancers and it should be considered evaluating the effect of VDR on cancer risk.


Assuntos
Neoplasias Ovarianas , Neoplasias da Próstata , Grupos Étnicos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina D
8.
Crit Rev Oncol Hematol ; 157: 103187, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33276181

RESUMO

We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85-3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26-3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75-6.63) and OS (SHR 3.91, 95 %CI 1.97-7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Between-estimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advanced-stage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33228006

RESUMO

We studied the determinants of motivation among post-menopausal women enrolled in a two-year diet and physical activity primary prevention randomized trial. Participants were requested to grade the importance attached to changing their lifestyle, their confidence about being able to implement the change, and their willingness to be involved in studies focusing on lifestyle. We used multi-adjusted regression to investigate the association between individual characteristics, study arm, and individual motivation at study entry and end. Participants (n = 234) were highly motivated both at entry and throughout the study. Women with pre-existing healthier eating habits and lifestyles (e.g., high consumption of fruit and vegetables, low red meat consumption, and physically active) were more motivated at entry and over the course of the study. Women assigned to any intervention arm were more motivated than those in the control arm. These findings may help enhance adherence to recommendations and improve effectiveness of community-based health promotion campaigns.

10.
Int J Infect Dis ; 102: 115-117, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075528

RESUMO

OBJECTIVES: Understanding the proportion of pandemic deaths captured as 'laboratory-confirmed' deaths is crucial. We assessed the ability of laboratory-confirmed deaths to capture mortality in the EU during the 2009 pandemic, and examined the likelihood that these findings are applicable to the SARS-CoV-2 pandemic. METHODS: We present unpublished results from the Global Pandemic Mortality (GLaMOR) project, in which country-specific mortality estimates were made for the 2009 influenza H1N1p pandemic. These estimates were compared with laboratory-confirmed deaths during the 2009 pandemic to estimate the ability of surveillance systems to capture pandemic mortality. RESULTS: For the 2009 influenza H1N1p pandemic, we estimated that the proportion of true pandemic deaths captured by laboratory-confirmed deaths was approximately 67%. Several differences between the two pandemics (e.g. age groups affected) make it unlikely that this capture rate will be equally high for SARS-CoV-2. CONCLUSION: The surveillance of laboratory-confirmed deaths in the EU during the 2009 pandemic was more accurate than previously assumed. We hypothesize that this method is less reliable for SARS-CoV-2. Near-real-time excess all-cause mortality estimates, routinely compiled by EuroMOMO, probably offer a better indicator of pandemic mortality. We urge more countries to join this project and that national-level absolute mortality numbers are presented.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33121070

RESUMO

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g., severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n = 12) found a significant increase in the risk of infection or in the illness severity or lethality, and some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.


Assuntos
Coinfecção/prevenção & controle , Infecções por Coronavirus , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral , Vacinação/efeitos adversos , Betacoronavirus , Coinfecção/diagnóstico , Coinfecção/epidemiologia , Controle de Doenças Transmissíveis , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Epidemias/prevenção & controle , Humanos , Vacinas contra Influenza/efeitos adversos , Influenza Humana/diagnóstico , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Vacinação/estatística & dados numéricos
12.
Melanoma Res ; 30(5): 500-510, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32898390

RESUMO

Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. We studied the association between MC1R variants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. We pooled individual data from 15 case-control studies conducted during 2005-2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. Six thousand eight hundred ninety-one CM cases and 5555 controls were included. CM risk was increased among MC1R variant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma (ALM), for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47-2.07) than intermittently (1.55, 95% CI 1.34-1.78) sun-exposed skin. CM risk was greater for those carrying 'R' vs. 'r' variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated with MC1R status. MC1R variants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin.

14.
Crit Rev Oncol Hematol ; 153: 103043, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32650217

RESUMO

INTRODUCTION: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN). METHODS: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN. RESULTS: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19-30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8-22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %-19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %-19 %] vs 7 %[95 %CI 3 %-12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %-25 %] vs 7%[95 %CI 3 %-13 %], p = 0.004). CONCLUSIONS: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS.


Assuntos
Neoplasias Encefálicas/radioterapia , Radiocirurgia/efeitos adversos , Irradiação Craniana , Humanos , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Estudos Retrospectivos , Resultado do Tratamento
15.
Eur J Epidemiol ; 35(11): 1057-1067, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710289

RESUMO

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose-response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03-1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02-1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04-1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01-1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02-1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose-response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

16.
Euro Surveill ; 25(23)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32553061

RESUMO

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.


Assuntos
Anticorpos Antivirais/sangue , Técnicas de Laboratório Clínico/métodos , Infecções por Coronaviridae/diagnóstico , Infecções por Coronavirus/diagnóstico , Coronavirus/imunologia , Pneumonia Viral/diagnóstico , Testes Sorológicos/normas , Síndrome Respiratória Aguda Grave/imunologia , Betacoronavirus , Técnicas de Laboratório Clínico/normas , Coronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Síndrome Respiratória Aguda Grave/sangue
17.
Cancer Epidemiol Biomarkers Prev ; 29(8): 1654-1664, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32467345

RESUMO

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; P trend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

18.
Head Neck ; 42(8): 2219-2220, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32149454
19.
Artigo em Inglês | MEDLINE | ID: mdl-32059496

RESUMO

Health literacy (HL) is an individual ability as well as a distributed resource available within an individual's social network. We performed an explorative study assessing the role of HL as the country-level ecological variable in predicting the health disparities among immigrants. Country-level HL data were obtained from the publicly available first European Health Literacy Survey reports. Individual-level data on citizenship, perceived health status, body mass index, smoking habits, physical activity and attendance at breast and cervical cancer screening were extracted from the European Health Interview Survey of Eurostat. Data from both sources were obtained for Austria, Bulgaria, Greece, Poland and Spain. The country-specific odds ratio (OR) for the association between the participants' citizenship and other individual health-relevant characteristics was pooled into summary OR using random-effects models. Meta-regression was used to explore whether the HL of a country could explain part of the between-countries heterogeneity. Results: For the perceived health status, nutritional status and attendance at cervical cancer screening, the lower was the country-level HL (as ecological variable), the higher were the health inequalities relating to citizenship. The results of our exploratory research suggest that improving the population HL may help mitigate health inequalities between residents and migrants.


Assuntos
Emigrantes e Imigrantes , Letramento em Saúde , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Neoplasias do Colo do Útero , Adolescente , Adulto , Áustria , Bulgária , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Espanha , Adulto Jovem
20.
Int J Cancer ; 146(12): 3267-3280, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31506954

RESUMO

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

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