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1.
Artigo em Inglês | MEDLINE | ID: mdl-32132151

RESUMO

BACKGROUND: We field tested new-to-market portable, digital applications to assess hearing, pulmonary, and cognitive function to determine the feasibility of implementing these applications across a range of age groups in the pilot phase of the 10,000 Families Study (10KFS), a new Minnesota family-based prospective cohort study. METHODS: We followed manufacturer recommended protocols for audiometry (SHOEBOX Inc), spirometry (NuvoAir) and the digital clock drawing test (dDCT) (Digital Cognition Technologies Inc). RESULTS: These digital devices were low cost and readily implemented in a 2.5-hour health fair visit with minimal training (2-3 hours) of study staff. To date, we have performed these measurements on 197 eligible 10KFS participants during an in-person clinic visit. A total of 37 children (age 4-17 years), 107 adults (18-64 years) and 53 seniors (65+ years) were eligible to undergo hearing and pulmonary assessments. Children were less likely to successfully complete the hearing test (76%) compared to adults (86%) and seniors (89%). However, successful completion of the pulmonary assessment was high across all groups: 100% of children and seniors, 98% of adults. The dCDT was performed among those over the age of 40, and completion rates were 92% for those aged 41-64 and 94% for those 65+ years. CONCLUSIONS: Our field testing indicates these digital applications are easy and cost-effective to implement in epidemiological studies. IMPACT: Digital applications provide exciting opportunities to collect data in population studies. Issues related to data privacy, data access and reproducibility of measurements need to be addressed before deploying digital applications in epidemiological studies.

2.
Cancer Res ; 80(5): 1210-1218, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. SIGNIFICANCE: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.

3.
Int J Cancer ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677159

RESUMO

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements.

4.
Gynecol Oncol ; 154(3): 608-615, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31303255

RESUMO

OBJECTIVE: Ovarian germ cell tumors (OGCT) are the primary ovarian malignancy affecting girls and young women. Globally, incidence rates and trends for OGCTs have not been compared in the literature and their etiology is not well described. Comparisons of incidence globally could inform etiologic hypotheses. The aim of this analysis was to evaluate geographic variation in OGCT incidence and to identify trends in incidence rates. METHODS: Data were extracted from Cancer Incidence in 5 Continents (CI5) from 1988 to 2012. Rates of OGCT in women and girls were calculated for ages 0-9, 10-19, and 20-39 years and standardized to the 2000-2025 average world population. Data were aggregated within subregions corresponding to the United Nations Statistics Division (UNSD) geoscheme. Incidence rates were compared in subregions and average annual percent change (AAPC) was estimated using Poisson regression. RESULTS: Overall, the highest incidence rates were observed in 10-19-year-olds. Incidence was generally the highest in Eastern Asia, Central America and North America. While incidence was variable by geographic region, less variation was observed in 0-9-year-olds as compared to adolescents and young adults. Significant increases in incidence were seen in some regions (Eastern Asia, Oceania, Western Europe, Southern Europe, and North America) and in countries with a high or very high human development index for one or more age groups. CONCLUSIONS: Evaluating 25 years of OGCT incidence data, the highest incidence rates and largest increases in incidence were seen in Eastern Asia. Future studies should focus on etiologic features that may account for geographic variation and increases in incidence of OGCT.


Assuntos
Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Ovarianas/epidemiologia , Adolescente , Adulto , Fatores Etários , América Central/epidemiologia , Europa (Continente)/epidemiologia , Extremo Oriente/epidemiologia , Feminino , Saúde Global , Humanos , Incidência , Estados Unidos/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
5.
Int J Cancer ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31304572

RESUMO

Survival differences by racial and ethnic group have been reported in children and adolescents with germ cell tumors (GCTs), but whether these differences depend on stage of disease is unclear. Using the SEER 18 registries (2000-2015), we examined GCT survival differences by race/ethnicity (non-Hispanic white [NHW], Black, Asian/Pacific Islander [API], Hispanic) separately for males and females aged 0-19 years at diagnosis. We used Kaplan-Meier survival curves (Log-Rank p values) to characterize survival differences. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between race/ethnicity and death. Using an inverse odds weighting mediation analysis, we estimated the association between race/ethnicity and death treating stage of disease as the mediator. There were no significant racial/ethnic survival differences among females. Male survival differed by race/ethnicity (p < 0.0001) with NHW males having the best survival. Compared to NHW, API and Hispanic males had significantly higher risks of death (API HR: 2.18; 95% CI: 1.32-3.56; Hispanic HR: 1.98; 95% CI: 1.42-2.78) (model adjusted for age and year at diagnosis, tumor histology and location, stage). This association was mediated by stage of disease only among Hispanic males with gonadal tumors (indirect HR: 1.18; 95% CI: 1.03-1.35). The increased risk of death after a testicular GCT diagnosis observed among Hispanic males was mediated by stage of disease. For API males and Hispanic males with extragonadal tumors, other unidentified factors including differences in exposures, tumor biology or treatment received may impact the observed racial/ethnic survival disparities.

6.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1502-1517, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31213463

RESUMO

BACKGROUND: The aim of this systematic review was to evaluate medical conditions and modifiable risk factors for myelodysplastic syndromes (MDS) using the 2001 or 2008 World Health Organization (WHO) diagnostic criteria. METHODS: PubMed, MEDLINE, and Scopus databases were searched for studies published between January 2001 and August 2017. Study characteristics and findings were abstracted for each article. RESULTS: Thirteen articles (4 cohort, 9 case-control) met the inclusion criteria. Smoking and alcohol use were each evaluated as potential MDS risk factors in four studies. Body mass index and anemia were each evaluated in two studies. Other potential risk factors evaluated in single studies included physical activity, dietary intake (tea, isoflavones, meat, fruit, or vegetables), history of allergies, autoimmune disorders and community-acquired infections, and use of antituberculosis drugs, traditional Chinese medicines, or hair dyes. CONCLUSIONS: Higher BMI, smoking, a history of autoimmune disorders, community-acquired infections, history of anemia, and use of antituberculosis drugs were associated with higher risk of MDS. Vigorous physical activity and tea and dietary isoflavone intake were associated with lower MDS risk. These findings suggest no association between the other factors and risk of MDS. IMPACT: Research on risk factors for MDS is limited, and further research in larger studies is needed.

7.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

8.
Eur J Haematol ; 103(1): 56-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31058390

RESUMO

OBJECTIVE: Little prospective data regarding factors determining patient outcomes in myelodysplastic syndromes (MDS) are available. To establish features of early mortality in MDS, we compare characteristics of patients dying within 1 year of diagnosis with those surviving longer. METHODS: We prospectively enrolled adults with a new MDS diagnosis in a population-based case-control study. Logistic regression was used to calculate odds ratios and 95% confidence intervals for potential predictors of early mortality. Subgroup analyses were conducted within the following groups: high-/very-high-risk IPSS-R; very-low-/low-/intermediate-risk IPSS-R; treated patients; and supportive care only patients. RESULTS: We observed early mortality in those with abnormal cytogenetics (OR: 3.36, 95% CI: 1.52-7.46), three or greater cytogenetic abnormalities (OR: 3.48, 95% CI: 1.51-7.99), treatment at a community medical center (versus academic) (OR: 2.55, 95% CI: 1.18-5.47), and with 2-3 concurrent medical comorbidities (OR: 2.14, 95% CI: 1.08-4.22). Similarly, in subgroup analyses, abnormal cytogenetics remained the main predictor of early mortality. CONCLUSION: Complex cytogenetics and prognostic risk category have been associated with early mortality without intervention. Our data confirm these associations in a large, prospectively followed cohort and highlight the significance of cytogenetic abnormalities and complexity regardless of IPSS-R risk categorization or treatment.


Assuntos
Síndromes Mielodisplásicas/epidemiologia , Idoso , Estudos de Casos e Controles , Aberrações Cromossômicas , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Razão de Chances , Vigilância da População , Prognóstico , Fatores Socioeconômicos
9.
J Natl Cancer Inst ; 111(12): 1263-1278, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

10.
JNCI Cancer Spectr ; 3(1): pkz007, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30984908

RESUMO

Background: Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from Cancer Incidence in 5 Continents (CI5) from 1988 to 2012 (CI5 volumes VII-XI). Methods: Rates of cancers in children ages 0-4 years were extracted from registries available in CI5 from 1988 to 2012. To overcome small numbers in individual registries, numerators and denominators were aggregated within regions corresponding to the United Nations' geoscheme. Average annual percent change (AAPC) was estimated using Poisson regression.  Robust standard errors were used in all models to correct for overdispersion in some regions, and 95% Wald confidence intervals and P values were reported. The top five cancers by increasing AAPC were ranked within each region. Results: Overall, in children under 5 years, increasing incidence was seen in multiple regions for acute lymphoblastic leukemia, acute myeloid leukemia, ependymal tumors, neuroblastoma, and hepatoblastoma. Hepatoblastoma had the largest AAPC in 11 out of 15 regions and showed an increase in all regions except southern Asia. Astrocytic tumors were the only cancer that decreased over the time period. Conclusions: We evaluated 25 years of cancer incidence in children ages 0-4 years and observed increases in incidence for hepatoblastoma, leukemia, neuroblastoma, and ependymal tumors. Further etiologic evaluation will be required to explain these increases in incidence.

11.
Pediatr Blood Cancer ; 66(6): e27620, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30815990

RESUMO

BACKGROUND: The male excess in childhood cancer incidence is well-established; however, the underlying biologic mechanisms remain unknown. Examining the association between male sex and childhood cancer by single year of age and tumor type may highlight important periods of risk such as variation in growth and hormonal changes, which will inform etiologic hypotheses. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2000-2015), incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated as the measure of association between male sex and childhood cancer by single year of age (0-19). RESULTS: The IRR for male cancer overall was 1.19 (95% CI, 1.18-1.20) and was similar in magnitude at nearly every year of age. Burkitt lymphoma was strongly associated with male sex (IRRs ≥2 at each year of age). Increased incidence was observed among males for acute lymphoblastic leukemia, Hodgkin and non-Hodgkin lymphomas for nearly all years of age. Medulloblastoma was the only central nervous system tumor with a significant male predominance at nearly every age. Male sex displayed a consistent inverse association with nephroblastoma and thyroid carcinoma over the ages studied. CONCLUSIONS: Male sex was positively associated with most cancers. The higher incidence rates observed in males remained consistent over the childhood and adolescent periods, suggesting that childhood and adolescent hormonal fluctuations may not be the primary driving factor for the sex disparities in childhood cancer. The observed incidence disparities may be due to sex differences in exposures, genetics, or immune responses.


Assuntos
Neoplasias/classificação , Neoplasias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Razão de Masculinidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/diagnóstico , Prognóstico , Programa de SEER , Estados Unidos/epidemiologia , Adulto Jovem
12.
Int J Cancer ; 145(1): 58-69, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561796

RESUMO

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Paridade , Gravidez , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia
13.
Cancer ; 124(19): 3900-3908, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30291793

RESUMO

BACKGROUND: Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there are no reports characterizing the prevalence of KS among male GCT cases. METHODS: The authors used array genotyping data from a Children's Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (433 males aged birth-19 years). Using Fisher's exact tests, the authors examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and several birth characteristics between cases of KS-GCT and GCT cases without chromosomal abnormalities. Using publicly available data, the authors estimated the 1-year risk, risk ratio, and corresponding 95% confidence interval of GCTs among KS cases. RESULTS: Based on analysis of array genotyping data, 3% of male GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS-GCT cases with parental questionnaire data (56%) reported a diagnosis of KS. No significant differences were observed with regard to patient or birth characteristics between KS-GCT and non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non-KS-GCT cases (P<.01). The authors estimated the risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males (risk ratio, 18.8; 95% confidence interval, 11.7-30.0). CONCLUSIONS: Compared with males without chromosomal abnormalities, males with KS are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT. In the current study, the authors report that approximately one-third of males with mediastinal germ cell tumors have Klinefelter syndrome, and therefore screening of these individuals for the syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely as males without Klinefelter syndrome to develop germ cell tumors.


Assuntos
Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/epidemiologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas/estatística & dados numéricos , Estudos de Coortes , Técnicas de Genotipagem , Homozigoto , Humanos , Lactente , Recém-Nascido , Padrões de Herança/genética , Síndrome de Klinefelter/genética , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/epidemiologia , Neoplasias do Mediastino/genética , Neoplasias Embrionárias de Células Germinativas/genética , Adulto Jovem
14.
Br J Cancer ; 119(7): 864-872, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30287918

RESUMO

BACKGROUND: Abnormal DNA methylation may be important in germ cell tumour (GCT) aetiology, as germ cells undergo complete epigenetic reprogramming during development. GCTs show differences in global and promoter methylation patterns by histologic subtype. We conducted an epigenome-wide study to identify methylation differences by GCT histology. METHODS: Using the Illumina HumanMethylation450K array we measured methylation in 154 paediatric GCTs (21 germinomas/seminomas/dysgerminoma, 70 yolk sac tumours [YST], 9 teratomas, and 54 mixed histology tumours). We identified differentially methylated regions (DMRs) between GCT histologies by comparing methylation beta values. RESULTS: We identified 8,481 DMRs (FWER < 0.05). Unsupervised hierarchical clustering of individual probes within DMRs resulted in four high level clusters closely corresponding to tumour histology. Clusters corresponding to age, location, sex and FFPE status were not observed within these DMRs. Germinomas displayed lower levels of methylation across the DMRs relative to the other histologic subtypes. Pathway analysis on the top 10% of genes with differential methylation in germinomas/seminomas/dysgerminoma compared to YST suggested angiogenesis and immune cell-related pathways displayed decreased methylation in germinomas/seminomas/dysgerminoma relative to YST. CONCLUSIONS: Paediatric GCT histologies have differential methylation patterns. The genes that are differentially methylated may provide insights into GCT aetiology including the timing of GCT initiation.


Assuntos
Metilação de DNA , Tumor do Seio Endodérmico/genética , Epigenômica/métodos , Germinoma/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Ovarianas/genética , Neoplasias Testiculares/genética , Adolescente , Criança , Pré-Escolar , Aprendizado Profundo , Disgerminoma/genética , Epigênese Genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise de Componente Principal , Regiões Promotoras Genéticas , Seminoma/genética
15.
Am J Gastroenterol ; 113(10): 1494-1505, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30177781

RESUMO

OBJECTIVE: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. DESIGN: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. RESULTS: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32-1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31-1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case-control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. CONCLUSIONS: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.


Assuntos
Neoplasias dos Ductos Biliares/epidemiologia , Colangiocarcinoma/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Hepáticas/epidemiologia , Obesidade/epidemiologia , Índice de Massa Corporal , Humanos , Incidência , Obesidade/diagnóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco
16.
Cancer Epidemiol ; 56: 106-111, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30130682

RESUMO

BACKGROUND: Testicular cancer is the most common cancer in young men in developed countries. In adults, international variation in testicular cancer incidence rates has been well-described, while previous research on pediatric and adolescent testicular cancer has been more geographically limited. METHODS: In this analysis, we used data from the three most recent volumes of Cancer Incidence in Five Continents (CI5) and the National Cancer Institute's SEER 18 registries to compare incidence rates for testicular cancer in children (ages 0-14) and adolescents and young adults (AYA; ages 15-39). RESULTS: We find that geographic incidence patterns in AYA are different from patterns in children under 15. In AYA, incidence is highest in Europe (137.4 per million), followed by Oceania (116.9 per million), North America (94.9 per million), South and Central America (66.5 per million), and lowest in Asia (27.1 per million). In contrast, childhood incidence is highest in Asia (4.2 per million) and South America (5.0 per million) and lowest in Europe (2.1 per million) and North America (2.5 per million). In the United States, patterns in incidence rates in racial and ethnic groups mirror international rates. CONCLUSION: These differences in incidence rate variations in pediatric and AYA testicular cancer are intriguing and may aid in understanding the different etiologies of testicular cancer by age group.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Neoplasias Testiculares/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Agências Internacionais , Masculino , Adulto Jovem
17.
Cancer ; 124(20): 4090-4097, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30125340

RESUMO

BACKGROUND: For many childhood cancers, survival is lower among non-Hispanic blacks and Hispanics in comparison with non-Hispanic whites, and this may be attributed to underlying socioeconomic factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival. METHODS: This study used population-based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000-2011 (n = 31,866). Black-white and Hispanic-white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census-tract composite index. RESULTS: Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES significantly mediated the race/ethnicity-survival association for acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and non-Hodgkin lymphoma; SES reduced the original association between race/ethnicity and survival by 44%, 28%, 49%, and 34%, respectively, for blacks versus whites and by 31%, 73%, 48%, and 28%, respectively, for Hispanics versus whites ((log hazard ratio total effect - log hazard ratio direct effect)/log hazard ratio total effect). CONCLUSIONS: SES significantly mediates racial/ethnic childhood cancer survival disparities for several cancers. However, the proportion of the total race/ethnicity-survival association explained by SES varies between black-white and Hispanic-white comparisons for some cancers, and this suggests that mediation by other factors differs across groups.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Grupos Étnicos/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Neoplasias/etnologia , Neoplasias/mortalidade , Classe Social , Adolescente , Adulto , Idade de Início , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Pré-Escolar , Grupos de Populações Continentais/etnologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/patologia , Programa de SEER , Fatores Socioeconômicos , Análise de Sobrevida , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
18.
Br J Cancer ; 118(7): 1005-1012, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29520041

RESUMO

BACKGROUND: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type. METHODS: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR≥7 drinks/day = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR≥5 drinks/day = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR>0-<0.5 drinks/day = 0.77, 95% CI: 0.67-0.89; HR>0.5-<1 drinks/day = 0.57, 95% CI: 0.44-0.73; HR1-<3 drinks/day = 0.71, 95% CI: 0.58-0.87), but not ICC. CONCLUSIONS: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias dos Ductos Biliares/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Colangiocarcinoma/epidemiologia , Neoplasias Hepáticas/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Ductos Biliares Intra-Hepáticos/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/efeitos adversos , Tabaco/efeitos adversos
19.
Cancer Epidemiol Biomarkers Prev ; 27(3): 348-351, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29339358

RESUMO

Background: Although some familial cancer syndromes include biliary tract cancers (BTCs; cancers of the gallbladder, intrahepatic and extrahepatic bile ducts, and ampulla of Vater), the few studies that have examined the relationships between family history of cancer (FHC) and BTCs have reported inconclusive findings. The objective of this study was to investigate the associations of FHC with risk of BTC in the Biliary Tract Cancers Pooling Project (BiTCaPP).Methods: We used Cox proportional hazards regressions models to estimate HRs and 95% confidence intervals for associations between FHC (any, first-degree, in female relative, in male relative, relative with gastrointestinal cancer, and relative with hormonally related cancer) and BTC risk by anatomic site within the biliary tract, adjusting for sex and race/ethnicity. Sensitivity analyses were conducted that restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy.Results: Data on FHC were available from 12 prospective studies within BiTCaPP, which collectively contributed 2,246 cases (729 gallbladder, 345 intrahepatic and 615 extrahepatic bile duct, and 385 ampulla of Vater cancers) with 21,706,107 person-years of follow-up. A marginal, inverse association between FHC and gallbladder cancer was driven to the null when analysis was restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy. FHC was not associated with risk of BTC at the other anatomic sites.Conclusions: These findings do not support an association between FHC and BTCs.Impact: In a study of 1.5 million people, FHC is not a risk factor for BTCs. Cancer Epidemiol Biomarkers Prev; 27(3); 348-51. ©2018 AACR.


Assuntos
Neoplasias do Sistema Biliar/epidemiologia , Anamnese/estatística & dados numéricos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
Br J Cancer ; 118(1): 121-126, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29065103

RESUMO

BACKGROUND: Studies of family history of cancer in paediatric germ cell tumours (GCTs) are few, and none has had sufficient sample size to specifically evaluate family history of GCT. METHODS: We utilised family history data from a paediatric GCT study to calculate standardised incidence ratios (SIR) for GCT and other cancers using age- and sex-specific incidence rates from the SEER Program. RESULTS: This analysis included 7998 relatives of paediatric GCT probands. We observed a higher number of GCT cases than expected in male and female relatives of probands (SIR=2.38, 95% CI 1.25, 3.51 for males; SIR=14.3, 95% CI 0.29, 28.4 for females). Further, we observed a particularly strong SIR for relatives of probands with intracranial GCT (SIR=8.07, 95% CI 3.51, 12.6). The SIR for relatives of probands with ovarian GCT was also elevated but did not reach statistical significance (SIR 4.35, 95% CI 0-9.27). Other notable associations include elevated SIRs for melanoma in male relatives and reduced SIRs for lymphatic/haematologic malignancies in male and female relatives. CONCLUSIONS: These results support the hypothesis that familial aggregation of GCT occurs in males and females.


Assuntos
Neoplasias Encefálicas/epidemiologia , Melanoma/epidemiologia , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Ovarianas/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Pais , Linhagem , Fatores Sexuais
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