Predicted leukocyte telomere length and risk of myeloid neoplasms.

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.

Rationale and design of CHD PULSE: Congenital Heart Disease Project to Understand Lifelong Survivor Experience.

BACKGROUND: With improved survival of adults with congenital heart disease (CHD) comes a need to understand the lifelong outcomes of this population. The aim of this paper is to describe the rationale and design of Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), a study to determine long-term medical, neurocognitive, and psychosocial outcomes among adults with a history of intervention for CHD and to identify factors associated with those outcomes. METHODS: CHD PULSE is a cross-sectional survey conducted from September 2021 to April 2023 among adults aged 18 and older with a history of at least 1 intervention for CHD at 1 of 11 participating U.S. centers in the Pediatric Cardiac Care Consortium. Participants with CHD were asked to complete a 99-question survey on a variety of topics including: demographics, surgeries, health insurance, health care, heart doctors, general health, height and weight, education and work history, reproductive health (for women only), and COVID-19. To construct a control group for the study, siblings of survey respondents were invited to complete a similar survey. Descriptive statistics for demographics, disease severity, center, and method of survey completion were computed for participants and controls. Comparisons were made between participants and non-participants to assess for response bias and between CHD participants and sibling controls to assess for baseline differences. RESULTS: Among the 14,322 eligible participants, there were 3,133 respondents (21.9%) from 48 U.S. states with surveys returned for inclusion in the study. Sibling contact information was provided by 691 respondents, with surveys returned by 326 siblings (47.2%). The median age of participants was 32.8 years at time of survey completion, with an interquartile range of 27.2 years to 39.7 years and an overall range of 20.1 to 82.9 years. Participants were predominantly female (55.1%) and of non-Hispanic White race/ethnicity (87.1%). There were no differences between participants and non-participants regarding severity of CHD. Compared to nonparticipants, participants were more likely to be female, of older age, and be of non-Hispanic White race/ethnicity. Enrolled siblings were more likely to be female and slightly younger than participants. CONCLUSIONS: With surveys from 3,133 participants from across the U.S., CHD PULSE is poised to provide keen insights into the lifelong journey of those living with CHD, extending beyond mere survival. These insights will offer opportunities for informing strategies to enhance and improve future outcomes for this population of patients.

Risk factors for de novo and therapy-related myelodysplastic syndromes (MDS).

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.

Alcohol use is not a significant contributor to myelodysplastic syndromes.

PURPOSE: Myelodysplastic syndromes (MDS) are a class of clonal neoplastic disorders of largely unknown etiology, and published data remain inconclusive regarding the association between lifetime alcohol consumption and MDS risk. In these analyses, data from a population-based case-control study were used to investigate this association. METHODS: Eligible cases of MDS were identified through the Minnesota Cancer Reporting System; controls were matched by sex and age-decile. A central review process was used to confirm MDS diagnosis and classify subtypes. Unconditional and polytomous logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Kaplan-Meier curves were used to compare survival by category of lifetime alcohol consumption. RESULTS: In total, 398 cases of MDS and 698 controls were included. Alcohol consumption at 23-30, 31-49, and 50-65 years of age, recent consumption 1 year before diagnosis/interview, and lifetime consumption were not found to be significantly associated with MDS in males (OR range 0.63-0.99) or females (OR range 0.58-1.70). Analysis by MDS subtype further suggested there was not a significant association between recent alcohol consumption and odds of disease by subtype (OR range 0.39-1.13). Lifetime alcohol consumption was not significantly associated with survival after diagnosis of MDS CONCLUSIONS: Previously reported associations between alcohol consumption and MDS risk were inconsistent. Results from our analyses by sex and disease subtype do not support alcohol as a significant contributor to risk of MDS.

Factors predicting early mortality after new diagnosis of myelodysplastic syndrome: A population-based study.

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.

Klinefelter syndrome in males with germ cell tumors: A report from the Children's Oncology Group.

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.

Family history of cancer in children and adolescents with germ cell tumours: a report from the Children's Oncology Group.

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.

Differences in DNA methylation profiles by histologic subtype of paediatric germ cell tumours: a report from the Children's Oncology Group.

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.

Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group.

Germ cell tumors (GCT) are a rare form of childhood cancer that originate from the primordial germ cell. Recent genome-wide association studies (GWAS) have identified susceptibility alleles for adult testicular GCT (TGCT). We test whether these SNPs are associated with GCT in pediatric and adolescent populations. This case-parent triad study includes individuals with GCT diagnosed between ages 0 and 19. We evaluated 26 SNPs from GWAS of adult TGCT and estimated main effects for pediatric GCT within complete trios (N = 366) using the transmission disequilibrium test. We used Estimation of Maternal, Imprinting and interaction effects using Multinomial modelling to evaluate maternal effects in non-Hispanic white trios and dyads (N = 244). We accounted for multiple comparisons using a Bonferroni correction. A variant in SPRY4 (rs4624820) was associated with reduced risk of GCT (OR [95% CI]: 0.70 [0.57, 0.86]). A variant in BAK1 (rs210138) was positively associated with GCT (OR [95% CI]: 1.70 [1.32, 2.18]), with a strong estimated effect for testis tumors (OR [95% CI]: 3.31 [1.89, 5.79]). Finally, a SNP in GAB2 (rs948662) was associated with increased risk for GCT (OR [95% CI]: 1.56 [1.20, 2.03]). Nominal associations (P < 0.05) were noted for eight additional loci. A maternal effect was observed for KITLG SNP rs4474514 (OR [95% CI]: 1.66 [1.21, 2.28]) and a paternal parent-of-origin effect was observed for rs7221274 (P = 0.00007), near TEX14, RAD51C, and PPM1E. We observed associations between SNPs in SPRY4, BAK1, and GAB2 and GCTs. This analysis suggests there may be common genetic risk factors for GCT in all age groups.

Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study.

Benzene exposure is one of the few well-established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) using population-based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self-report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR = 1.77, 95% CI 1.19, 2.63 and OR = 2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR = 2.05, 95% CI 1.15, 3.63 and OR = 2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions and coal dust were associated with AML (range ORs = 2.68-4.03), while no association was seen between these exposures and MDS (range ORs = 0.57-1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population-based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases.

Association between mitochondrial DNA haplogroup and myelodysplastic syndromes.

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non-Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS-R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population-based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.

Factors associated with hematopoietic cell transplantation (HCT) among patients in a population-based study of myelodysplastic syndrome (MDS) in Minnesota.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective erythropoiesis, and an increased risk of developing acute myeloid leukemia. Treatment planning for patients with MDS is a complex process, and we sought to better characterize hematopoietic cell transplantation (HCT) outcomes and the factors that play into decision-making regarding referral of adults with MDS for definitive therapy with HCT. Patients enrolled in a population-based study of MDS between April 2010 and January 2013 who underwent HCT within the first year after enrollment were included in this analysis. Age- and risk-matched MDS patient controls also enrolled during that time period were used as a comparison. Survival was significantly better in the HCT group (48 vs. 21 %, log-rank p value 0.009). Non-HCT patients were more likely to have comorbidities, and HCT patients were more likely to have a college degree and an income >$80,000. All three of these variables were independently associated with HCT, but none impacted survival. Patients with MDS in our study who underwent HCT had better survival than a comparable group of patients who did not undergo HCT. With refined treatment techniques, more patients may be able to be considered for this therapy. More work needs to be done to determine why education and income appear to impact the decision to pursue HCT, but these factors may impact referral to an academic center where aggressive therapy like HCT is more likely to be considered.

Remote Field Application of Digital Technology for Hearing Assessments in a Cohort of Pediatric Germ Cell Tumor Survivors.

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 epidemiologic studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor 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 κ. 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)]. The mean assessment length was 37.6 minutes, and the 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 × 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 geographic areas.

Recovering from traumatic occupational hand injury following surgery: a biopsychosocial perspective.

PURPOSE: Significant differences occur in the return-to-work (RTW) period amongst workers with an acute traumatic occupational hand injury. This study aimed to develop and test a comprehensive multivariate conceptual biopsychosocial model to predict RTW outcome. METHOD: Patients presenting with an occupational hand injury were interviewed 7-10 days after their injury (N = 192) and again at 4 weeks after their injury (n = 150). Potential determinants from biomedical, work-related, demographic and psychosocial categories were studied simultaneously. RESULTS: A small sub-set of workers with an acute traumatic hand injury experienced chronic disability beyond 12 weeks. Analyzing the relationship between predictor variables and work absence resulted in the identification of the most important determinants of recovery. During the acute stages of recovery, injury severity, pain, self-efficacy, and living alone were the most important determinants of delayed RTW outcome. At 4 weeks post-injury, locus of control, injury severity, negative affect and living alone were the most important predictors of delayed RTW. CONCLUSION: A number of prognostic variables were identified that influenced RTW outcome, which offer new and unique contributions to the field. Injury severity was not the most important determinant of RTW outcome; neither were factors identified in previous hand injury research, such as attribution of blame, significant predictors. Factors not examined in previous research, such as negative affect, were more important determinants of delayed RTW.

Women's desires for mental health support following a pregnancy loss, termination of pregnancy for medical reasons, or abortion: A report from the STRONG Women Study.

OBJECTIVE: We report on women's mental health care desires following a miscarriage, medical termination, or abortion. METHOD: 689 women completed a questionnaire on reproductive history, health care following miscarriage/medical termination/abortion, and current mental health. Descriptive statistics and logistic regression analyses examined: miscarriage/termination/abortion incidence, desires for mental health support following miscarriages/terminations/abortions, and current mental health. RESULTS: Of 365 women with a pregnancy history, 37% reported ≥1 miscarriage, 9% ≥1 medical termination, 16% ≥1 abortion, and 3% endorsed all three. Current mental health did not differ between women with a history of miscarriage/termination/abortion and those with only live births (p = 0.82). Following miscarriage, 68% of women discussed options for the medical management of pregnancy loss with their provider, 32% discussed grief/loss, and 25% received mental health care recommendations. Engagement in mental health services was reported by 16% of women with a history of miscarriage, 38% after medical termination, and 19% following an abortion. Of women who became pregnant after their most recent miscarriage/termination/abortion and did not receive mental health care, 55% wished they had received services during the subsequent pregnancy. CONCLUSIONS: Women desire mental health care after miscarriages, medical terminations, or abortions, warranting improved access to mental health care for these individuals.

Evaluation of the Association Between Congenital Cytomegalovirus Infection and Pediatric Acute Lymphoblastic Leukemia.

Importance: Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer, and a leading cause of death in children. Understanding the causes of pediatric ALL is necessary to enable early detection and prevention; congenital cytomegalovirus (cCMV) has recently been identified as a potential moderate-to-strong factor associated with risk for ALL. Objective: To compare the prevalence of cCMV infection between ALL cases and matched controls. Design, Setting, and Participants: In this population-based case-control study of ALL cases and matched controls, cases consisted of children aged 0 to 14 years between 1987 and 2014 with an ALL diagnosis identified through the Michigan Cancer Surveillance Program and born in Michigan on or after October 1, 1987. Cancer-free controls were identified by the Michigan BioTrust for Health and matched on age, sex, and mother's race and ethnicity. Data were analyzed from November to May 2022. Exposures: cCMV infection measured by quantitative polymerase chain reaction in newborn dried blood spots. Main Outcomes and Measures: ALL diagnosed in children aged 0 to 14 years. Results: A total of 1189 ALL cases and 4756 matched controls were included in the study. Bloodspots were collected from participants at birth, and 3425 (57.6%) participants were male. cCMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%). There was no difference in the odds of cCMV infection comparing ALL cases with controls (odds ratio, 1.30; 95% CI, 0.52-3.24). Immunophenotype was available for 536 cases (45.1%) and cytogenetic data for 127 (27%). When stratified by subtype characteristics, hyperdiploid ALL (74 cases) was associated with 6.26 times greater odds of cCMV infection compared with unmatched controls (95% CI, 1.44-27.19). Conclusions and Relevance: In this case-control study of cCMV and pediatric ALL, cCMV was associated with increased risk of hyperdiploid ALL. These findings encourage continued research.

Medical conditions and risk of adult myeloid leukemia.

PURPOSE: Although a few previous studies have reported positive associations between adult myeloid leukemia and a history of certain medical conditions, the etiology of most cases remains largely unknown. Our purpose was to examine associations between certain medical conditions and adult myeloid leukemia. METHODS: Using logistic regression, we evaluated associations between 16 self-reported medical conditions and myeloid leukemia in a case-control study of 670 cases [including 420 acute myeloid leukemia (AML) and 186 chronic myelogenous leukemia (CML)] and 701 population-based controls. RESULTS: We observed significant positive associations between AML and ulcerative colitis (odds ratio (OR) = 3.8; 95 % confidence interval (CI), 1.1-13) and between CML and peptic ulcer (OR = 2.0; 95% CI, 1.1-3.8). A personal cancer history increased both AML (OR = 2.6; 95% CI, 1.7-3.9) and CML (OR = 3.5; 95% CI, 2.0-5.8) risk even after excluding individuals who reported prior radiation and/or chemotherapy treatment. CONCLUSION: Certain inflammatory medical conditions and a personal history of cancer, independent from therapy, are associated with an increased risk of myeloid leukemia.

Personal history of autoimmune disease and other medical conditions and risk of myelodysplastic syndromes.

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.

High prevalence of asymptomatic CMV shedding in healthy children attending the minnesota state fair.

BACKGROUND: Young children in the household are a known risk factor for maternal CMV infection and consequently, congenital infection in infants. However, little is known about viral shedding in pre-school aged children. OBJECTIVES: To estimate the prevalence of CMV DNA shedding and CMV antibodies among healthy children and their mothers. STUDY DESIGN: A study of children ages 0 through 5 years was undertaken at the 2019 Minnesota State Fair. Children and their mothers were assessed for CMV shedding by procurement of a saliva swab for CMV PCR testing. An optional finger-stick for capillary blood was used to assess CMV antibodies. RESULTS: A total of 109 children and 85 mothers were enrolled. The prevalence of CMV saliva shedding among children (mean age 3.1 years, SE=0.16) and their mothers was 12/109 (11.0%) and 1/85 (1.2%), respectively. The prevalence of CMV DNA among children peaked at 3 years of age (26%) while the mean viral load was greatest at one year of age (236,693 IU/mL). CMV IgG antibodies among those who agreed to a finger-stick were detected in 16/35 mothers (45.7%) and 0/7 children (0%). Mothers of children aged 5 years or greater had the highest seroprevalence (61.5%). CONCLUSIONS: The prevalence of CMV salivary shedding in this unselected sample of young children was approximately 11.0%. The overall maternal seroprevalence in our sample was <50%, suggesting these women are at risk for acquisition of a primary CMV infection in subsequent pregnancies.

Growth Hormone Deficiency in Childhood Intracranial Germ Cell Tumor Survivors.

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.