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BACKGROUND: Women aged ≥40 years diagnosed with a malignant ovarian germ cell tumor are more likely to have poor outcomes than their younger counterparts (aged 15-39 years). OBJECTIVE: We used the National Cancer Database (NCDB) to evaluate patterns of care and overall survival for individuals diagnosed with one of the four most common histologic subtypes of malignant ovarian germ cell tumor by age group. METHODS: We identified women aged 15-90 diagnosed with ovarian germ cell tumors in the NCDB (2004-2016). Logistic regression was used to compare patterns of care, demographic, and disease characteristics by age group. Cox proportional hazards regression was used to evaluate associations between a range of demographic, clinical, and treatment characteristics with overall survival. RESULTS: A total of n=2998 patients who were diagnosed with one of the four most common histologic subtypes (immature teratoma, dysgerminoma, yolk sac tumor, and mixed germ cell) of ovarian germ cell tumor were included in the analysis. Patients aged ≥40 years diagnosed with ovarian germ cell tumors were more likely to have co-morbidities, a bilateral tumor, higher stage of disease, receive chemotherapy only, and have a residual tumor after resection as compared with patients aged <40 years. Moreover, women aged ≥40 years had the highest risk of death (reference: 15-24 year olds; HR=5.37, 95% CI 3.76 to 7.66) after adjustment for demographic characteristics, tumor histology, and treatment received. In stratified analyses, women aged ≥40 years had significantly worse overall survival at each disease stage and histologic subtype. CONCLUSION: Findings suggest that women aged ≥40 years who are diagnosed with ovarian germ cell tumors have worse overall survival than those aged <40, independent of stage, disease characteristics, and treatment. Our study highlights the need for future research to better understand reasons for poorer outcomes in women aged ≥40 years.
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BACKGROUND: Childhood cancer survivors treated with platinum-based chemotherapy are at risk of treatment-induced hearing loss. Accurate evaluation of hearing thresholds has historically been limited to clinical audiometry, which is logistically challenging and expensive to include in epidemiological studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor (GCT) survivors treated with platinum-based chemotherapy. METHODS: Survivors from the GCT Outcomes and Late effects Data (GOLD) study were recruited to the pilot study (n=100). Study personnel conducted remote hearing assessments of standard and extended high frequency thresholds using validated tablet-based audiometry (SHOEBOX Inc). T-tests and Wilcoxon rank-sum tests evaluated differences in assessment characteristics between children and adults. Agreement between self-reported and measured hearing loss was calculated using Cohen's kappa. RESULTS: We were able to reach 136/168 (81%) eligible participants, of which 100 (74%) agreed to participate. Successful completion of the remote hearing assessment was high (97%; 20 children [ages 7-17], 77 adults [ages 18-31]). Mean assessment length was 37.6 minutes and mean turnaround time was 8.3 days. We observed hearing loss at standard frequencies in 21% of participants. Agreement between self-reported and measured hearing loss was significant (p-value = 1.41 x 10-7), with 83.5% concordance. CONCLUSIONS: Hearing loss measured using the remote assessment aligns with self-reporting and rates of hearing loss reported in the literature for this population. IMPACT: Remote application of tablet-based audiometry is a feasible and efficacious method for measuring hearing in epidemiologic studies with participants spread across large geographical areas.
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BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.
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Neoplasias do Sistema Biliar , Café , Chá , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/etiologia , Idoso , Incidência , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/etiologia , Neoplasias da Vesícula Biliar/prevenção & controle , Fatores de Risco , Adulto , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/etiologiaRESUMO
Innovations in the care of adolescent and young adult (AYA) germ cell tumors (GCTs) are needed for one of the most common AYA cancers for which treatment has not significantly changed for several decades. Testicular GCTs (TGCTs) are the most common cancers in 15- to 39-year-old men, and ovarian GCTs (OvGCTs) are the leading gynecologic malignancies in women younger than 25 years. Excellent outcomes, even in widely metastatic disease using cisplatin-based chemotherapy, can be achieved since Einhorn and Donohue's landmark 1977 study in TGCT. However, as the severity of accompanying late effects (ototoxicity, neurotoxicity, cardiovascular disease, second malignant neoplasms, nephrotoxicity, and others) has emerged, efforts to deintensity treatment and find alternatives to cisplatin have taken on new urgency. Current innovations include the collaborative design of clinical trials that accrue GCTs across all ages and both sexes, including adolescents (previously on pediatric trials), and OvGCT (previously on gynecologic-only trials). Joint trials accrue larger sample sizes at a faster rate and therefore evaluate new approaches more rapidly. These joint trials also allow for biospecimen collection to further probe GCT etiology and underlying mechanisms of tumor growth, thus providing new therapeutic options. This AYA approach has been fostered by The Malignant Germ Cell International Consortium, which includes over 115 GCT disease experts from pediatric, gynecologic, and genitourinary oncologies in 16 countries. Trials in development incorporate, to our knowledge, for the first time, molecular risk stratification and precision oncology approaches on the basis of specific GCT biology. This collaborative AYA approach pioneering successfully in GCT could serve as a model for impactful research for other AYA cancer types.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Criança , Adulto , Cisplatino , Sobrevivência , Medicina de Precisão , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/terapia , GenômicaRESUMO
Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS.
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Estudo de Associação Genômica Ampla , Leucemia Mieloide Aguda , Humanos , Predisposição Genética para Doença , Fatores de Risco , Leucócitos/metabolismo , Estratificação de Risco Genético , Telômero/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Análise da Randomização MendelianaRESUMO
The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood. Members of the COG Epidemiology Committee have also been involved in other large-scale National Institutes of Health efforts, including the Childhood Cancer Data Initiative and the Gabriella Miller Kids First Pediatric Research Program, which are improving our understanding of the factors associated with childhood cancer risk. Future plans will focus on addressing questions surrounding health disparities, utilizing novel biospecimens in COG epidemiology studies, exploring the role of environmental factors on the etiologies and outcomes of childhood cancer, collaborating with other COG committees to expand the role of epidemiology in childhood cancer research, and building new epidemiologic studies from the Molecular Characterization Initiative-all with the ultimate goal of developing novel prevention and intervention strategies for childhood cancer.
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Neoplasias Ósseas , Neoplasias , Osteossarcoma , Rabdomiossarcoma , Sarcoma de Ewing , Criança , Humanos , Neoplasias/epidemiologia , OncologiaRESUMO
Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.
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Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas , Adolescente , Adulto Jovem , Criança , Humanos , Neoplasias Embrionárias de Células Germinativas/terapia , Oncologia , Biomarcadores Tumorais , Fatores de RiscoRESUMO
BACKGROUND: Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics. METHODS: Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial). RESULTS: Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females. CONCLUSIONS: These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereas males with nonsyndromic defects and females are not at an increased risk. PLAIN LANGUAGE SUMMARY: We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes. We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs. Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs. Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.
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Síndrome de Down , Síndrome de Klinefelter , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Criança , Humanos , Adolescente , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genéticaRESUMO
Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.
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Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Masculino , Criança , Lactente , Feminino , Adulto Jovem , Humanos , Adolescente , Recém-Nascido , Pré-Escolar , Adulto , Via de Sinalização Wnt/genética , Neoplasias Embrionárias de Células Germinativas/genética , Teratoma/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , GenômicaRESUMO
Background and Aims: Intracranial germ cell tumor (iGCT) survivors have multiple risk factors for growth hormone (GH) deficiency, a commonly reported late effect in childhood cancer survivors. The objective of this study is to examine the prevalence of GH deficiency among childhood iGCT survivors. Methods: Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), a case parent triad study conducted using the Children's Oncology Group registry protocols, including 216 cases with iGCTs. Data on late effects and outcomes are available for 129 iGCT cases who consented for a follow-up study including a self-administered questionnaire and medical record retrieval. GH deficiency was identified via self-report and validated through medical record review. Chi-squared and Fisher's exact tests were used to examine cases with GH deficiency predating iGCT detection. Logistic regression was used to identify predictors of GH deficiency as a late effect. Results: Of 129 iGCT cases who participated in the late effects study, 45% had GH deficiency; 18% had GH deficiency predating the iGCT and 27% developed GH deficiency within a median of 19 months after diagnosis. Younger age at diagnosis, suprasellar location, and higher radiation doses were associated with GH deficiency as a late effect. Conclusions: GH deficiency is highly prevalent as an early clinical sign for iGCT and frequently arises as an early late effect after treatment. Additional investigation is needed to address earlier detection and treatment for this highly prevalent late effect in iGCT survivors.
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BACKGROUND: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. METHODS: Paediatric GCT samples were obtained from a Children's Oncology Group study and state biobank programs in California and Michigan (N = 1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups. RESULTS: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR = 0.82; P = 0.0003), TERT/rs2853677-G (OR = 0.80; P = 0.001), and TERT/rs7705526-A (OR = 0.81; P = 0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults. CONCLUSION: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.
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Neoplasias Embrionárias de Células Germinativas , Telômero , Adulto , Criança , Feminino , Humanos , Leucócitos , Neoplasias Embrionárias de Células Germinativas/genética , Telômero/genética , Homeostase do Telômero/genéticaRESUMO
BACKGROUND: Autoimmune diseases and hematopoietic malignancies are known to cluster within individuals, suggesting intertwined etiologies. A limited number of studies have evaluated pre-existing medical conditions as risk factors for myelodysplastic syndromes (MDS). We evaluated associations between autoimmune disease and other medical conditions and risk of MDS. METHODS: Cases were identified through the Minnesota Cancer Reporting System. Controls were identified through the Minnesota State driver's license/identification card list. History of autoimmune disease and other medical conditions was based on self-report; proxy interviews were not conducted. Unconditional logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: We included 395 cases and 694 controls. Cases were significantly more likely to report a diagnosis of any autoimmune disease when compared with controls (aOR=1.41, 95% CI: 1.05-1.89) after adjustment for age, sex, education, NSAID use, exposure to benzene and body mass index. When we evaluated specific autoimmune conditions, a statistically significant association was observed for hypothyroidism (aOR=2.16, 95% CI: 1.39-3.34) and odds ratios were elevated for inflammatory bowel disease (aOR=1.75) and systemic lupus erythematosus (SLE; aOR=3.65), although these associations did not reach statistical significance. Presence of an autoimmune condition did not impact overall survival (p = 0.91). CONCLUSION: Our results validate previous findings of an association between autoimmune disease and MDS. Further studies are required to determine whether this association is due to shared etiology, treatment for autoimmune diseases, or altered immune surveillance or bone marrow damage caused by the autoimmune condition.
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Doenças Autoimunes , Síndromes Mielodisplásicas , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Estudos de Casos e Controles , Humanos , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/etiologia , Razão de Chances , Fatores de RiscoRESUMO
Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative.
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COVID-19 , Informática Médica , Neoplasias , Adolescente , Criança , Ciência de Dados , Humanos , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , SARS-CoV-2 , Adulto JovemRESUMO
BACKGROUND: Disparities in survival by race/ethnicity, socioeconomic status (SES), and geography in adolescent and young adult (AYA) patients with central nervous system (CNS) tumors have not been well studied. PROCEDURE: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was conducted for AYA patients diagnosed with primary CNS tumors. Adjusted hazard ratios (aHR) were calculated using a multivariate Cox proportional hazard model to evaluate the association between race/ethnicity, SES, rurality, and hazard of death. RESULTS: All minority groups showed an increased hazard of death with greatest disparities in the high-grade glioma cohort. Lower SES was associated with an increased hazard of death in non-Hispanic White (NHW) patients (aHR 1.12; 95% confidence interval [CI] 1.01-1.24), non-Hispanic Black (NHB) patients (aHR 1.34; 95% CI 1.00-1.80), and patients aged 25-29 years (aHR 1.29; 95% CI 1.07-1.55). Mediation analysis showed an indirect effect of SES on the effect of race/ethnicity on the hazard of death only among NHB patients, with SES accounting for 33.7% of the association between NHB and hazard of death. Rurality was associated with an increased hazard of death for patients in the lowest SES tertile (aHR 1.31; 95% CI 1.08-1.59) and NHW patients (aHR 1.20; 95% CI 1.08-1.34). CONCLUSIONS: Patients identified as a racial/ethnic minority, patients with a lower SES, and patients residing in rural areas had an increased hazard of death. Further studies are needed to understand and address the biological, psychosocial, societal, and economic factors that impact AYA neuro-oncology patients at highest risk of experiencing poorer outcomes.
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Neoplasias do Sistema Nervoso Central , Etnicidade , Adolescente , Neoplasias do Sistema Nervoso Central/epidemiologia , Minorias Étnicas e Raciais , Humanos , Grupos Minoritários , Estudos Retrospectivos , Programa de SEER , Classe Social , Taxa de Sobrevida , Adulto JovemRESUMO
Myelodysplastic syndromes (MDS) are a heterogeneous group of blood disorders. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a chemopreventive effect in some cancers. We evaluated associations between NSAID use and MDS in a population-based case-control study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Secondary analyses stratified by sex and MDS subtype were also conducted.The analysis included 399 MDS cases and 698 controls. No significant associations between MDS and use of aspirin (OR = 0.87, 95% CI 0.67-1.14), ibuprofen (OR = 0.91, 95% CI 0.64-1.30), acetaminophen (OR = 1.29, 95% CI 0.90-1.84) or NSAIDs overall (OR = 0.92, 95% CI 0.68-1.23) were observed. No significant associations were observed in models stratified by sex or MDS subtype; however, the direction of the effect between NSAID use and MDS varied by MDS subtype. Our results do not support an association between NSAID use and MDS overall.
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Síndromes Mielodisplásicas , Preparações Farmacêuticas , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Casos e Controles , Humanos , Minnesota/epidemiologia , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/epidemiologia , Fatores de RiscoRESUMO
PURPOSE: Myelodysplastic syndromes (MDS) are classified as de novo and therapy-related (tMDS). We evaluated associations between MDS risk factors separately for de novo and tMDS. METHODS: The study population included 346 de novo MDS cases, 37 tMDS cases and 682 population controls frequency matched by age and sex. Polytomous logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjustment, former smoking status (OR = 1.45, 95% CI: 1.10-1.93), personal history of autoimmune disease (OR = 1.34, 95% CI: 0.99-1.82) and exposure to benzene (OR = 1.48, 95% CI: 1.00-2.19) were associated with de novo MDS. Risk estimates for the associations between smoking, autoimmune disease, and benzene exposure were similar in magnitude but non-significant in tMDS cases. Among individuals with a previous diagnosis of cancer, de novo MDS cases and controls were more likely to have had a previous solid tumor, while tMDS cases more commonly had a previous hematologic malignancy. CONCLUSIONS: We observed similar associations between smoking, history of autoimmune disease and benzene exposure in de novo and tMDS although estimates for tMDS were imprecise due to small sample sizes. Future analyses with larger sample sizes will be required to confirm whether environmental factors influence risk of tMDS.
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Síndromes Mielodisplásicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Doenças Autoimunes/epidemiologia , Benzeno/toxicidade , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Fatores de Risco , Fumar/epidemiologiaRESUMO
Genomewide association studies (GWAS) have been widely used in recent years to identify common variants that are associated with multiple types of cancer, including testicular germ cell tumors. These studies require no a priori hypotheses and have advantages, including the ability to highlight new pathways relevant to the biology of common diseases. GWAS require collection of germline DNA from individuals with and without the disease of interest. Following DNA extraction and quantification, a variety of array based platforms are available to evaluate common and moderately rare germline variation throughout the genome in an agnostic fashion. Here, we describe DNA extraction methods from samples typically used in the evaluation of germline genetic variation (blood and saliva). We also describe assays used to assess DNA quality and quantity. Finally, we include methods describing array based genotyping using the Illumina platform and validation of relevant variants using the iPLEX Agena Multiplexed Genotyping (formerly Sequenom).
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Alelos , Biomarcadores Tumorais , Estudo de Associação Genômica Ampla/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida/métodos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Saliva/metabolismo , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiologiaRESUMO
BACKGROUND: Central nervous system (CNS) tumours comprise 20% of childhood cancers worldwide. Whether childhood CNS tumour incidence has increased over time across geographic regions remains to be explored. METHODS: We identified CNS cancers in the Cancer in Five Continents (CI5) data and estimated age standardized incidence rates (ASRs; cases/million children) and 95% confidence intervals (95% CI), male-to-female incidence rate ratios (IRR; 95% CI) and average annual percent change in incidence (AAPC; 95% CI) by geographic region for children aged 0-19 years where data were available using Poisson regression and generalized estimating equations (GEE). Cancers included: astrocytic tumours, medulloblastoma, ependymal, oligodendroglial and mixed glioma, glioma of uncertain origin, and other embryonal tumours. Geographic regions were defined using the United Nations geoscheme. RESULTS: There were 56 468 CNS cancers included in the study. ASRs were highest for astrocytic tumours globally in 2012 (ASR: 5.83; 95% CI: 5.68-5.99). Globally, all cancers exhibited a male excess in incidence. Regionally, only medulloblastoma had a consistently elevated male-to-female IRR at 1.4-2.2. Globally, incidence decreased for astrocytic tumours in GEE models (AAPC: -1.66; 95% CI: -3.04 to -0.26) and increased for medulloblastoma (AAPC 0.66; 95% CI: 0.19-1.14), ependymal tumours (AAPC: 1.49; 95% CI: 1.49; 95%: 0.69-2.30), glioma of uncertain origin (AAPC: 4.76; 95% CI: 1.17-1.14) and other embryonal tumours (AAPC: 3.58; 95% CI: 2.03-5.15). Regional variation in incidence trends was observed. Countries moving from lower to higher Human Development Index (HDI) over time did not appear to drive observed incidence trends. CONCLUSIONS: Epidemiologic and molecular studies on underlying mechanisms for changes in the global incidence of CNS tumours are necessary.
Assuntos
Neoplasias do Sistema Nervoso Central , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Adulto JovemRESUMO
BACKGROUND: Epidemiologic analyses of sarcoma are limited by the heterogeneity and rarity of the disease. Utilizing population-based surveillance data enabled us to evaluate the contribution of census tract-level socioeconomic status (CT-SES) and race/ethnicity on sarcoma incidence rates. METHODS: We utilized the Surveillance, Epidemiology, and End Results program to evaluate associations between CT-SES and race/ethnicity on the incidence rates of sarcoma. Incidence rate ratios and 99% confidence intervals were estimated from quasi-Poisson models. All models were stratified by broad age groups (pediatric: <20 years, adult: 20-65 years, older adult: 65+ years) and adjusted for sex, age, and year of diagnosis. Within each age group, we conducted analyses stratified by somatic genome (fusion-positive and fusion-negative sarcomas) and for subtypes with >200 total cases. A P value less than 0.01 was considered statistically significant. RESULTS: We included 55,415 sarcoma cases in 35 sarcoma subtype-age group combinations. Increasing CT-SES was statistically significantly associated with 11 subtype-age group combinations, primarily in the older age group strata (8 subtypes), whereas malignant peripheral nerve sheath tumors in adults were associated with decreasing CT-SES. Nearly every sarcoma subtype-age group combination displayed racial/ethnic disparities in incidence that were independent of CT-SES. CONCLUSIONS: We found race/ethnicity to be more frequently associated with sarcoma incidence than CT-SES. Our findings suggest that genetic variation associated with ancestry may play a stronger role than area-level SES-related factors in the etiology of sarcoma. IMPACT: These findings provide direction for future etiologic studies of sarcomas.