Chang JS, Tsai CR, Tsai YW, Wiemels JLMedically diagnosed infections and risk of childhood leukaemia: a population-based case-control study. Int J Epidemiol 41(4): 1050-1059

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
International Journal of Epidemiology (Impact Factor: 9.18). 07/2012; 41(4):1050-9. DOI: 10.1093/ije/dys113
Source: PubMed


Previous studies on the association between childhood infections and childhood leukaemia have produced inconsistent results, likely due to the recall error/bias of infection data reported by the parents. The current study used a population-based and record-based case-control design to evaluate the association between childhood leukaemia and infections using the National Health Insurance Research Database of Taiwan.
In all, 846 childhood acute lymphoblastic leukaemia (ALL) and 193 acute myeloid leukaemia (AML) patients newly diagnosed between 2000 and 2008, aged >1 and <10 years, were included. Up to four controls (3374 for ALL and 766 for AML) individually matched to each case on sex, birth date and time of diagnosis (reference date for the controls) were identified. Conditional logistic regression was performed to assess the association between childhood leukaemia and infections.
Having any infection before 1 year of age was associated with an increased risk for both childhood ALL (odds ratio = 3.2, 95% confidence interval 2.2-4.7) and AML (odds ratio = 6.0, 95% confidence interval 2.0-17.8), with a stronger risk associated with more episodes of infections. Similar results were observed for infections occurring >1 year before the cases' diagnosis of childhood leukaemia.
Children with leukaemia may have a dysregulated immune function present at an early age, resulting in more episodes of symptomatic infections compared with healthy controls. However, confounding by other infectious measures such as birth order and day care attendance could not be ruled out. Finally, the results are only relevant to the medically diagnosed infections.

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    • "In this study, we conducted a SNP-association analysis of childhood BCP-ALL compared with controls across a 4 Mb stretch of the xMHC in an attempt to pinpoint regions of potential involvement in susceptibility. The xMHC is a potentially strong candidate region for a role in genetic susceptibility to childhood ALL, a disease whose causation has been attributed to an inappropriate immune response to post-natal infection [2,24,25]. Using a validated panel of greater than 1,100 SNPs designed to capture the genetic diversity of this complex genomic region, we identified two loci associated with childhood BCP-ALL risk. After correction for multiple testing, we found a statistically significant increased risk associated with the minor allele of rs9296068 in proximity to the HLA-DOA gene. "
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    ABSTRACT: The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.
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    ABSTRACT: BACKGROUND:: Statins have been postulated to prevent infection through immunomodulatory effects. OBJECTIVES:: To compare the incidence of infections in statin users to that in nonusers within the same health care system. METHODS:: This was a retrospective cohort study of patients enrolled as Tricare Prime or Plus in the San Antonio military multimarket. Statin users were patients who received a statin for at least 3 months between October 1, 2004 and September 30, 2005. Nonusers were patients who did not receive a statin within the study period (October 1, 2003-September 30, 2009). Inpatient and outpatient International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to determine the incidence of infections during the follow-up period (October 1, 2005-September 30, 2009) via multivariable regression analysis and time to infection via Cox regression analysis. RESULTS:: Of 45,247 patients who met the study criteria, 12,981 (29%) were statin users and 32,266 were nonusers. After adjustments for age, gender, Charlson Comorbidity Score, tobacco use, alcohol abuse/dependence, health care utilization and use of specific medication classes, statin use was associated with an increased incidence of common infections (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.06-1.19) but not influenza or fungal infections (OR: 1.06, 95% CI: 0.80-1.39; OR: 0.97; 95% CI: 0.91-1.04, respectively). Time-to-first infection was similar in statin users and nonusers in all infection categories examined. CONCLUSIONS:: Statin use was associated with an increased incidence of common infections but not influenza or fungal infections. This study does not support a protective role of statins in infection prevention; however, the influence of potential confounders cannot be excluded.
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