ABSTRACT
BACKGROUND: Maternal smoking during pregnancy has been often implicated in the development of childhood leukemia with ambiguous results. Hence, we conducted a meta-analysis aiming to summarize current evidence and quantify any tentative impact. PROCEDURE: We retrieved one cohort (553 leukemias compared to 1,440,542 children), 20 case-control studies and also analyzed the updated Greek case-control dataset with unpublished data, yielding in total 11,092 cases and 25,221 controls. RESULTS: Odds ratios reported in the studies included ranged from 0.70 to 2.20 for acute lymphocytic (ALL) and from 0.60 to 2.17 for acute myelocytic leukemia (AML). The combined effect regarding the association of maternal smoking (any vs. no) and leukemia risk was 1.03 for ALL (95% CI = 0.95-1.12, random effects model) and 0.99 for AML (95% CI = 0.90-1.09, fixed effects model). The results remained unchanged when sensitivity analyses were undertaken of studies reporting same maternal smoking periods, those focusing only on childhood leukemia deaths or investigations which did not clearly define AML subtype. CONCLUSIONS: The findings of the meta-analysis challenge the limits of traditional epidemiology to provide sound inferences when point estimates of constituent studies range around the null. In particular, this study provides no support to a hypothesis linking maternal smoking during pregnancy with subsequent development of main childhood leukemia subtypes. Further investigations employing molecular and genetic epidemiology, however, might be needed in the hope to reveal even minimal risks pertaining individuals with specific susceptibility to tobacco compounds who sustain high environmental exposures prenatally or postnatally.
Subject(s)
Leukemia, Myeloid, Acute/etiology , Prenatal Exposure Delayed Effects/etiology , Smoking/adverse effects , Adolescent , Case-Control Studies , Child , Child, Preschool , Female , Greece/epidemiology , Humans , Infant , Infant, Newborn , Leukemia, Myeloid, Acute/epidemiology , Male , Matched-Pair Analysis , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Risk , Smoking/epidemiologyABSTRACT
Currently, carcinogenesis is considered to be the result of mal-expression of tumour suppressor genes and oncogenes, leading either way to uncontrollable and disorganized cell mitosis. Recently a novel class of genes has drawn the interest of the scientific community. These are microRNAs (miRNAs), a class of noncoding RNAs, 20-23 nucleotides in length, that can up or downregulate gene expression of downstream gene targets (including transcription factors, oncogenes, and tumour suppressor genes) at the post-transcriptional level. Some members of this new class of genes seem to have the potential to act simultaneously either as oncogenes or as tumour suppressor genes depending on the molecular microenvironment of the cell. We elaborate on this hypothesis by giving examples of miRNAs (e.g. mir-9, miR-17-92) which seem to function by the abovementioned mechanism. This could mean that the deterministic notion of carcinogenesis as a result of merely tumour suppressor genes and oncogenes deregulation could be revised to contain the fact that certain members of this novel class of genes have the potential to play both roles simultaneously.
