Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population-based study in Utah and Norway.

BACKGROUND: In this study, we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumors in the central nervous system (CNS), and leukemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. METHODS: We used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. RESULTS: The overall incidence of CNS tumors increased with consecutive birth cohorts similarly in Utah and Norway (both P < 0.001). Incidence rates of leukemia were more stable and similar in both Utah and in Norway with 4.6/100 000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumors was significantly associated with risk of childhood CNS tumors in Utah HR = 3.05 (95% CI 1.80-5.16) and Norway HR = 2.87 (95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukemia had high risk of leukemia (HR = 2.39, 95% CI 1.61-3.55). CONCLUSION: Despite geographical distance and assumed large lifestyle differences, two genetically linked pediatric populations show similar incidences of CNS tumors and leukemia in the period 1966-2015. CNS tumors and leukemia aggregated in families in both countries.

The relationship between leukemia and TP53 gene codon Arg72Pro polymorphism: analysis in a multi-ethnic population.

Aim: Many studies have analyzed the relationship between Arg72Pro polymorphism of TP53 and leukemia; nevertheless, the findings continue to be indeterminate. We, therefore, performed an updated meta-analysis in multi-ethnic groups using specialized software for genome-wide association studies meta-analysis. Materials & methods: PubMed, EMBASE and Google Scholar were searched up to October 2018. An odds ratio (OR) with the corresponding 95% CI was used to evaluate the strength in the association. Results: This meta-analysis included 16 studies with 2337 cases and 9494 controls. In the overall population, significant relationship between Arg72Pro polymorphism of TP53 and leukemia susceptibility was found in two genetic models (recessive model: OR = 1.276, 95% CI = 1.102-1.476; p = 0.01; overdominant model: OR = 0.891, 95% CI = 0.802-0.988; p = 0.03). In stratified studies with ethnicity, a significant association was found in five ethnic groups, including Chinese, Americans, Africans, Japanese and Indians. Conclusion: We demonstrated that an association exist between leukemia risk and TP53 gene codon Arg72Pro polymorphism in the recessive and overdominant genetic models. Also, our findings show that the TP53 Arg72Pro polymorphism may influence leukemia development in different populations.

Effects of GST null genotypes on individual susceptibility to leukemia: A meta-analysis.

BACKGROUND: Whether glutathione S-transferases (GST) null genotypes influence individual susceptibility to leukemia remains controversial. Thus, we performed this meta-analysis to better analyze potential influences of GST null genotypes on individual susceptibility to leukemia. METHODS: Literature retrieve was conducted in PubMed, Web of Science and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally fifty-one studies were enrolled for analyses. Significant associations with elevated individual susceptibility to leukemia were detected for GSTM1 (p < .0001, OR = 1.28, 95%CI 1.16-1.41), GSTP1 (p = .003, OR = 1.22, 95%CI 1.07-1.40) and GSTT1 (p < .0001, OR = 1.53, 95%CI 1.35-1.74) null genotypes in overall analyses. Further subgroup analyses by type of disease revealed that GSTM1, GSTP1 and GSTT1 null genotypes were all significantly associated with elevated individual susceptibility to acute lymphoblastic leukemia, GSTM1 and GSTT1 null genotypes were significantly associated with elevated individual susceptibility to acute myeloid leukemia, and GSTT1 null genotype was also significantly associated with elevated individual susceptibility to chronic leukemia. When we stratified data according to ethnicity of participants, positive results were found for all investigated variants in Caucasians and West Asians. Additionally, GSTM1 null genotype was also significantly correlated with elevated individual susceptibility to leukemia in East Asians. CONCLUSIONS: Our findings indicated that GSTM1, GSTT1 and GSTP1 null genotypes might serve as potential genetic biomarkers of leukemia in certain ethnicities.

Graft-versus-Host Disease after HLA-Matched Sibling Bone Marrow or Peripheral Blood Stem Cell Transplantation: Comparison of North American Caucasian and Japanese Populations.

The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality.

Overview of the National Occupational Mortality Surveillance (NOMS) system: leukemia and acute myocardial infarction risk by industry and occupation in 30 US states 1985-1999, 2003-2004, and 2007.

BACKGROUND: Cancer and chronic disease are leading causes of death in the US with an estimated cost of $46 billion. METHODS: We analyzed 11 million cause-specific deaths of US workers age 18-64 years in 30 states during 1985-1999, 2003-2004, and 2007 by occupation, industry, race, gender, and Hispanic origin. RESULTS: The highest significantly elevated proportionate leukemia mortality was observed in engineers, protective service, and advertising sales manager occupations and in banks/savings &loans/credit agencies, public safety, and public administration industries. The highest significantly elevated smoking-adjusted acute myocardial infarction mortality was noted in industrial and refractory machinery mechanics, farmers, mining machine operators, and agricultural worker occupations; and wholesale farm supplies, agricultural chemical, synthetic rubber, and agricultural crop industries. CONCLUSIONS: Significantly elevated risks for acute myocardial infarction and leukemia were observed across several occupations and industries that confirm existing reports and add new information. Interested investigators can access the NOMS website at http://www.cdc.gov/niosh/topics/NOMS/.

Etoposide quinone is a covalent poison of human topoisomerase IIß.

Etoposide is a topoisomerase II poison that is utilized to treat a broad spectrum of human cancers. Despite its wide clinical use, 2-3% of patients treated with etoposide eventually develop treatment-related acute myeloid leukemias (t-AMLs) characterized by rearrangements of the MLL gene. The molecular basis underlying the development of these t-AMLs is not well understood; however, previous studies have implicated etoposide metabolites (i.e., etoposide quinone) and topoisomerase IIß in the leukemogenic process. Although interactions between etoposide quinone and topoisomerase IIα have been characterized, the effects of the drug metabolite on the activity of human topoisomerase IIß have not been reported. Thus, we examined the ability of etoposide quinone to poison human topoisomerase IIß. The quinone induced ~4 times more enzyme-mediated DNA cleavage than did the parent drug. Furthermore, the potency of etoposide quinone was ~2 times greater against topoisomerase IIß than it was against topoisomerase IIα, and the drug reacted ~2-4 times faster with the ß isoform. Etoposide quinone induced a higher ratio of double- to single-stranded breaks than etoposide, and its activity was less dependent on ATP. Whereas etoposide acts as an interfacial topoisomerase II poison, etoposide quinone displayed all of the hallmarks of a covalent poison: the activity of the metabolite was abolished by reducing agents, and the compound inactivated topoisomerase IIß when it was incubated with the enzyme prior to the addition of DNA. These results are consistent with the hypothesis that etoposide quinone contributes to etoposide-related leukemogenesis through an interaction with topoisomerase IIß.

Graft-versus-host disease and survival after cord blood transplantation for acute leukemia: a comparison of Japanese versus White populations.

An earlier report identified higher risks of acute and chronic graft-versus-host disease (GVHD) in White children compared with the Japanese after HLA-matched sibling transplantations. The current analysis explored whether racial differences are associated with GVHD risks after unrelated umbilical cord blood transplantation. Included are patients of Japanese descent (n = 257) and Whites (n = 260; 168 of 260 received antithymocyte globulin [ATG]). Transplants were performed in the United States or Japan between 2000 and 2009; patients were aged 16 years or younger, had acute leukemia, were in complete remission, and received a myeloablative conditioning regimen. The median ages of the Japanese and Whites who received ATG were younger at 5 years compared with 8 years for Whites who did not receive ATG. In all groups most transplants were mismatched at 1 or 2 HLA loci. Multivariate analysis found no differences in risks of acute GVHD between the Japanese and Whites. However, chronic GVHD was higher in Whites who did not receive ATG compared with the Japanese (hazard ratio, 2.16; P < .001), and treatment-related mortality was higher in Whites who received ATG compared with the Japanese (relative risk, 1.81; P = .01). Nevertheless, there were no significant differences in overall survival between the 3 groups.

XRCC1 Arg399Gln variation and leukemia susceptibility: evidence from 2,647 cases and 5,518 controls.

Previous reports implicate XRCC1 Arg399Gln polymorphism as a possible risk factor for several cancers. Increasing studies have been conducted on the association of XRCC1 Arg399Gln polymorphisms with susceptibility to leukemia. However, conflicting results have been generated. The goal of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of XRCC1 Arg399Gln variation with leukemia were conducted, and subgroup analyses on ethnicity and clinical types were further performed. Eligible studies were identified for the period up to February 2013. Consequently, 16 publications including 17 case-control studies with 2,647 cases and 5,518 controls were selected for analysis. The overall data indicated a significant association of XRCC1 Arg399Gln polymorphism with leukemia risk (Gln/Gln versus Arg/Arg: OR = 1.37, 95% confidence interval (CI) = 1.08-1.74; dominant model: OR = 1.23, 95%CI = 1.03-1.46; recessive model: OR = 1.23, 95%CI = 1.06-1.44). In the subgroup analysis by ethnicity, Gln allele may increase leukemia susceptibility among Asians (Gln/Gln versus Arg/Arg: OR = 1.82, 95%CI = 1.19-2.78; dominant model: OR = 1.53, 95%CI = 1.00-2.33; recessive model: OR = 1.51, 95%CI = 1.11-2.06), but not Caucasians or mixed ethnicities. In the subgroup analysis by clinical types, increased risk was observed in acute lymphocytic leukemia (ALL) subgroup (Gln/Gln versus Arg/Arg: OR = 1.45, 95%CI = 1.09-1.93; recessive model: OR = 1.30, 95%CI = 1.00-1.69), but not in acute myeloid leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia subgroups, respectively. Collectively, the results of the present study suggest that XRCC1 Arg399Gln polymorphism might be a low-penetrant risk factor for leukemia, particularly among Asians. Homozygous Gln/Gln alleles might have a correlation with increased ALL susceptibility.

Racial and ethnic associations with comprehensive cancer center access and clinical trial enrollment for acute leukemia.

BACKGROUND: Clinical trial participation at Comprehensive Cancer Centers (CCC) is inequitable for minoritized racial and ethnic groups with acute leukemia. CCCs care for a high proportion of adults with acute leukemia. It is unclear if participation inequities are due to CCC access, post-access enrollment, or both. METHODS: We conducted a retrospective cohort study of adults with acute leukemia (2010-2019) residing within Massachusetts, the designated catchment area of the Dana-Farber/Harvard Cancer Center (DF/HCC). Individuals were categorized as non-Hispanic Asian (NHA), Black (NHB), White (NHW), Hispanic White (HW), or Other. Decomposition analyses assessed covariate contributions to disparities in (1) access to DF/HCC care and (2) post-access enrollment. RESULTS: Of 3698 individuals with acute leukemia, 85.9% were NHW, 4.5% HW, 4.3% NHB, 3.7% NHA, and 1.3% Other. Access was lower for HW (age- and sex-adjusted OR = 0.64, 95% CI = 0.45 to 0.90) and reduced post-access enrollment for HW (aOR = 0.54, 95% CI =0.34 to 0.86) and NHB (aOR = 0.60, 95% CI = 0.39 to 0.92) compared to NHW. Payor and socioeconomic status (SES) accounted for 25.2% and 21.2% of the +1.1% absolute difference in HW access. Marital status and SES accounted for 8.0% and 7.0% of the -8.8% absolute disparity in HW enrollment; 76.4% of the disparity was unexplained. SES and marital status accounted for 8.2% and 7.1% of the -9.1% absolute disparity in NHB enrollment; 73.0% of the disparity was unexplained. CONCLUSIONS: A substantial proportion of racial and ethnic inequities in acute leukemia trial enrollment at CCCs are from post-access enrollment, the majority of which was not explained by sociodemographic factors.

Significance of ethnicity in the risk of acute graft-versus-host disease and leukemia relapse after unrelated donor hematopoietic stem cell transplantation.

The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient-donor pairs from the International Histocompatibility Working Group in HCT met the following 3 criteria: (1) HLA-A, -B, -C, -DRB1, and -DQB1 allele matched donor, (2) diagnosis of leukemia, and (3) non-T cell depleted GVHD prophylaxis. Posttransplantation risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, white, African American, Hispanic, and Native American patients that underwent transplantation from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II to IV and 15.3% grades III to IV; non-Japanese Asian patients: 42.1% grades II to IV and 15.7% grades III to IV) compared with white patients (56.5% grades II to IV and 22.6% grades III to IV) (P < .001). The hazard ratio of acute GVHD for white patients was significantly higher than for Japanese patients. Unexpectedly, the hazard ratio of leukemia relapse in white patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background.

Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups.

The survival of younger patients with acute leukemia has improved in the early 21(st) century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21(st) century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes.

Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes.

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 10(7)/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used.

Racial, socioeconomic, and demographic disparities in access to fertility preservation in young women diagnosed with cancer.

BACKGROUND: This study seeks to examine the relation between sociodemographic characteristics and the utilization of fertility preservation services in reproductive age women diagnosed with cancer. METHODS: A total of 1041 women diagnosed with cancer between the ages of 18 and 40 years responded to a retrospective survey on demographic information and reproductive health history. Five cancer types were included: leukemia, Hodgkin disease, non-Hodgkin lymphoma, breast cancer, and gastrointestinal cancer. Nine hundred eighteen women reported treatment with potential to affect fertility (chemotherapy, pelvic radiation, pelvic surgery, or bone marrow transplant). Student t test, linear regression, and multivariate logistic regression were used where appropriate to determine the relation between sociodemographic characteristics and the odds of using fertility preservation services. RESULTS: Sixty-one percent of women were counseled on the risk of cancer treatment to fertility by the oncology team. Overall, 4% of women pursued fertility preservation. In multivariate analysis, women who had not attained a bachelor's degree (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9) were less likely to be counseled. Trends also suggested possible disparities in access to fertility preservation with age older than 35 years (OR, 0.1; 95% CI, 0.0-1.4) or previous children (OR, 0.3; 95% CI, 0.1-1.1) at diagnosis. Disparities in access to fertility preservation based on ethnicity and sexual orientation were also observed. CONCLUSIONS: Sociodemographic health disparities likely affect access to fertility preservation services. Although awareness of fertility preservation has improved in the past decade, an unmet need remains for reproductive health counseling and fertility preservation in reproductive age women diagnosed with cancer.

Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia.

Dominant-negative (DN) Ikaros isoforms, having important roles in pathogenesis of leukemia, are mainly studied in pediatric patients, but little is known about Chinese adult patients. We examined 339 Chinese adult patients with leukemia and demonstrated the different findings between our results and those in several previous studies showing that DN isoforms overexpressed in Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)ALL) and lymphoid/mixed blast crisis of chronic myelogenous leukemia. We confirmed that deletion of IKZF1 gene exons 4-7 is responsible for the generation of Ikaros 6 (Ik6). Moreover, we observed that expression of DN isoforms was dynamically consistent with BCR-ABL1 transcript levels, associated with higher incidence of relapse within 3 months or poor response to induction chemotherapy in Ph(+)ALL, correlated with high white blood cell, blast cells, CD34 positive cells, and delayed achieving complete hematological remission in ALL patients. In conclusion, this study provides a rationale for the integration of aberrant Ikaros isoforms, notably Ik6 and Ik10, in the evaluation of adult ALL, particularly in Ph(+)ALL patients.

Measuring health-related quality of life in leukemia: the Functional Assessment of Cancer Therapy--Leukemia (FACT-Leu) questionnaire.

OBJECTIVE: Develop and validate a health-related quality-of-life (measure for patients with acute and chronic leukemia. METHODS: The study consisted of two phases: scale construction and scale validation. For the item-generation phase, a summary of the literature combined with qualitative results from item-generation interviews with 29 acute or chronic leukemia patients and 16 health care providers yielded an initial item pool reflecting leukemia-specific concerns and symptoms. Items underwent iterations of review and reduction according to defined retention criteria to support content validity, as defined by priority concerns of patients. Seventeen final leukemia-specific items were combined with the Functional Assessment of Cancer Therapy-General to create the FACT-Leukemia (FACT-Leu) scale. For the validation phase, 79 individuals with acute or chronic leukemia completed questionnaires at three time points. RESULTS: All FACT-Leu subscale and aggregated scores showed high internal consistency (αs ranging from 0.75 to 0.96). Test-retest reliability was adequate for all subscales (intraclass correlation range 0.765-0.890). The FACT-Leu scale demonstrated good convergent validity, with significant correlations with quality-of-life criteria and performance status, in the expected direction. FACT-Leu subscale scores were significantly different among the three performance status change groups, suggesting good responsiveness to change. CONCLUSIONS: The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease.

Population versus hospital controls for case-control studies on cancers in Chinese hospitals.

BACKGROUND: Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. METHODS: We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. RESULTS: The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. CONCLUSIONS: The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting.

Association between Ataxia Telangiectasia Mutated gene polymorphisms and childhood leukemia in Taiwan.

The ataxia telangiectasia mutated (ATM) gene plays a major role in repairing the double-strand breaks and maintaining the genome stability. In this case-control study, associations of seven ATM single-nucleotide polymorphisms (rs600931, rs189037, rs652311, rs624366, rs228589, rs227092 and rs227060) with risks in childhood leukemia in a Taiwanese population were investigated. Two hundred and sixty-six patients with childhood leukemia and 266 age-matched healthy controls recruited were genotyped and analyzed. The P-values of the distributions of the genotypic frequencies in the seven ATM polymorphisms were 0.8925, 0.2835, 0.5772, 0.8731, 0.3641, 0.9181 and 0.5071, respectively. The Pvalues of the distributions of the allelic frequencies in the seven ATM polymorphisms were 0.6158, 0.1179, 0.6971, 0.7944, 0.1887, 0.6605 and 0.2747, respectively. Although the results did not indicate that ATM polymorphism is directly associated with childhood leukemia, the gene-gene and gene-environment interactions of ATM with other factors is worthy of further investigation in the future.

Geographic and ethnic differences in childhood leukaemia and lymphoma survival: comparisons of Philippine residents, Asian Americans and Caucasians in the United States.

BACKGROUND: Childhood cancer survival estimates from developing nations are rare. METHODS: Using the US SEER and the Manila and Rizal Cancer Registry databases in the Philippines, 5-year survival for childhood leukaemia and lymphoma in 2001-2005 among Asian Americans were compared with both Filipinos and Caucasians in the United States. Estimates for patients in the United States in earlier time periods were compared with that of Philippine residents to estimate delay in achievements of comparable levels of survival. RESULTS: Childhood leukaemia and lymphoma relative survival was much lower in Filipinos living in the Philippines (32.9 and 47.7%) than in Asian Americans (80.1 and 90.5%) and Caucasians (81.9 and 87%). Achievement of comparable survival rates of Philippine residents lagged behind by 20 to >30 years compared with patients in the United States. CONCLUSIONS: The large differences in survival estimates of US populations and Philippine residents highlight the deficiencies of paediatric cancer care delivery in the Philippines. The long survival lag underlines the need for major improvements in access to diagnostic and treatment facilities.

Pediatric leukemia could be driven predominantly by non-synonymous variants in mitochondrial complex V in Mizo population from Northeast India.

Leukemia is the most common childhood malignancy and studies had been carried out with promising revelations in its diagnosis and prognosis. However, majority of the studies are focused on nuclear alterations, while mitochondrial mutations are not well studied. Although there are studies of mitochondrial mutations in the adult leukemias, it does not represent the same for childhood malignancy. This is the first scientific report on the mtDNA mutational pattern of pediatric leukemic cases from a endogamous tribal population in Northeast India. ATP6 involved in the Complex V was found to be more altered with respect to the Non-synonymous variants. mtDNA variations in the non-coding region (D-Loop - g.152 T>C) and in the coding region (MT-ND2, g.4824 A>G, p.T119A) showed a maternal inheritance which could reveal a genetic predisposition with lower penetrance. D-Loop variant (g.152 T>C) could be a diagnostic marker in accordance with previous report but is in contrast to pertaining only in AML - M3 subtype rather was found across in myeloid malignancies.

Risk factors associated with suicide among leukemia patients: A Surveillance, Epidemiology, and End Results analysis.

Previous studies have found that the risk of suicide is higher in patients diagnosed with cancer than in the general population. We aimed to identify potential risk factors associated with suicide in leukemia patients by analyzing data obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We screened the SEER database for leukemia patients added between 1975 and 2017, and calculated their suicide rate and standardized mortality rate (SMR) relative to the total United States population from 1981 to 2017 as a reference. Univariate and multivariate Cox regression analyses were used to determine the risk factors for suicide in leukemia patients. We collected 142,386 leukemia patients who had been added to the SEER database from 1975 to 2017, of whom 191 patients committed suicide over an observation period of 95,397 person-years. The suicide rate of leukemia patients was 26.41 per 100,000 person-years, and hence the SMR of the suicided leukemia patients was 2.16 (95% confidence interval [CI] = 1.85-2.47). The univariate and multivariate Cox regression analyses showed that a high risk of suicide was associated with male sex (vs. female: hazard ratio [HR] = 4.41, 95% CI = 2.93-6.63, p < 0.001), older age at diagnosis (60-69 years vs. ≤39 years: HR = 2.60, 95% CI = 1.60-4.23, p < 0.001; 70-79 years vs. ≤39 years: HR = 2.84, 95% CI = 1.72-4.68, p < 0.001; ≥80 years vs. ≤39 years: HR = 2.94, 95% CI = 1.65-5.21, p < 0.001), white race (vs. black: HR = 6.80, 95% CI = 1.69-27.40, p = 0.007), acute myeloid leukemia (vs. lymphocytic leukemia: HR = 1.59, 95% CI = 1.09-2.33, p = 0.016), unspecified and other specified leukemia (vs. lymphocytic leukemia: HR = 2.72, 95% CI = 1.55-4.75, p < 0.001), and living in a small city (vs. large city: HR = 2.10, 95% CI = 1.23-3.60, p = 0.007). Meanwhile, being a non-Hispanic black (vs. Hispanic: HR = 0.06, 95% CI = 0.01-0.62, p = 0.019) was a protective factor for suicide. Male sex, older age at diagnosis, white race, and acute myeloid leukemia were risk factors for suicide in leukemia patients, while being a non-Hispanic black was a protective factor. Medical workers should, therefore, provide targeted preventive measures to leukemia patients with a high risk of suicide.