A population-based case-control study of childhood leukemia in Shanghai

A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio [OR] = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.     

Family cancer history and risk of childhood acute leukemia (France)

OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.     

Family history of hematopoietic and other cancers in children with acute lymphoblastic leukemia

It has been difficult to show a genetic contribution for many cancers, resulting in the belief that rare cancers such as leukemia are sporadic. We carried out a population-based case-control study including 701 incident cases of acute lymphoblastic leukemia (ALL) aged 0-14 years and diagnosed between 1980 and 1998 in Québec (Canada); 701 healthy controls were matched on age and sex. Cancer family history in the child's relatives was reported by parents. A positive family history of hematopoietic malignancies among first- or second-degree relatives was associated with a slight increase of risk for childhood ALL (odds ratio 2.06; 95% confidence interval=1.22-3.49); the excess was attributable to second-degree relatives, and observed for grandparents as well as for uncles/aunts. The risk of ALL was not increased in children with a family history of cancers other than hematopoietic cancers. The data suggest a modest familial contribution to childhood ALL.     

Maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia： a meta-analysis

Objective: The authors used a meta-analytic technique to quantify the evidence of an association between ma-ternal alcohol consumption during pregnancy and childhood acute leukemia (AL), which provided a basis for the prevention of childhood AL. Methods: Relevant literatures of maternal alcohol consumption during pregnancy were comprehensively searched and screened. Subgroup meta-analysis was conducted according to the type of leukemia. Results of research data of maternal alcohol consumption during pregnancy were tested for heterogeneity. Combined OR values and 95% CIs were statistically calculated with RevMan 4.2 software; Funnel plots were applied to conduct bias analysis for those included litera-tures. Results: Ten related literatures were included after data screening, 4593 cases in Al. group and 6157 cases in control group respectively. According to heterogeneity test result (χ2=16.26, P<0.05), the combined OR values and 95% Cl were calculated with random effects model, which were 1.02(0.92-1.14), Z=0.41, P=0.68 > 0.05, indicating that there was no significant difference between maternal alcohol consumption during pregnancy and the risk of childhood acute leukemia (AL). Subgroup analysis: for the association between maternal alcohol consumption dudng pregnancy and childhood acute lympho-blastic leukemia (ALL), the combined OR value and 95% CI were 0.92 (0.84-1.00), Z=1.92, P=0.05, indicating that there was significant difference between two groups; for the association between maternal alcohol consumption during pregnancy and childhood acute non-lymphoblastic leukemia (ANLL), the combined OR values and 95% Cl were 0.82 (0.61-1.11), Z=1.30, P=0.19>0.05, indicating that there was no significant difference between two groups. Conclusion: Maternal alcohol consumption during pregnancy is a risk factor in childhood ALL, but not in childhood ANLL.     

Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring.

Parental exposure to hydrocarbons at work has been suggested to increase the risk of childhood leukemia. Evidence, however, is not entirely consistent. Very few studies have evaluated the potential parental occupational hazards by exposure time windows. The Children's Cancer Group recently completed a large-scale case-control study involving 1842 acute lymphocytic leukemia (ALL) cases and 1986 matched controls. The study examined the association of self-reported occupational exposure to various hydrocarbons among parents with risk of childhood ALL by exposure time window, immunophenotype of ALL, and age at diagnosis. We found that maternal exposure to solvents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.3-2.5] and paints or thinners (OR, 1.6; 95% CI, 1.2-2.2) during the preconception period (OR, 1.6; 95% CI, 1.1-2.3) and during pregnancy (OR, 1.7; 95% CI, 1.2-2.3) and to plastic materials during the postnatal period (OR, 2.2; 95% CI, 1.0-4.7) were related to an increased risk of childhood ALL. A positive association between ALL and paternal exposure to plastic materials during the preconception period was also found (OR, 1.4; 95% CI, 1.0-1.9). The ALL risk associated with parental exposures to hydrocarbons did not vary greatly with immunophenotype of ALL. These results suggest that the effect of parental occupational exposure to hydrocarbons on offspring may depend on the type of hydrocarbon and the timing of the exposure.     

Familial history of cancer and childhood acute leukemia: a French population-based case-control study.

A case-control study was conducted to investigate the role of a familial history of cancer in the etiology of childhood acute leukemia. The history of cancer in the relatives of 472 cases was compared with that of 567 population-based controls. Recruitment was frequency matched on age, sex and region. The familial history of cancer in each child's relatives was reported by the mother in response to a standardized self-administered questionnaire. A familial history of solid tumor in first or second-degree relatives was associated with an increased risk of acute lymphoblastic leukemia (odds ratio (OR)=1.6 [95% confidence interval, 1.2-2.1]), while a familial history of hematopoietic malignancies in first or second-degree relatives was associated with an increased risk of acute myeloid leukemia (OR=4.3 [1.4-13]). The ORs for the histories of cancer increased with the number of relatives with cancer (OR=1.5 [1.1-2.0] for one relative and OR=2.3 [1.3-3.8] for two relatives or more; Ptrend<0.0001). Significant associations between childhood acute leukemia and familial history of genital cancers and brain tumor were also observed (OR=2.7 [1.2-5.8] and OR=10.7 [1.3-86], respectively). This study supports the hypothesis that a familial history of cancer may play a role in the etiology of childhood acute leukemia. It also evidences some specific associations that require further investigation.     

Risk of Acute Lymphoblastic Leukemia: Results of a Case-Control Study

Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Differentenvironmental factors might be effective in the occurrence of this malignancy during childhood. The aim of this studywas to find environmental risk factors in childhood ALL in Hamadan, Iran. Methods: This case-control study wasdone in 2015-2018 on 125 children younger than 15 years of age suffering from ALL. Patients were matched with130 controls with respect to age, gender, and residence location. The identification of risk factors for ALL was soughtbased on the comparison of studied variables between case and control individuals. Results: A statistically significantincreased risk for ALL was found with regard to type of delivery (OR: 0.43, 95% CI: 0.20 - 0.92, p˂0.02), childcare(OR: 4.58, 95% CI: 0.95 - 22.20, p˂0.04), birth weight (OR: 1.44, 95% CI: 1.53 - 2.21, p˂0.006), father’s educationlevel (OR: 2.67, 95% CI: 1.10 - 6.45, p˂0.02), and father’s job (OR: 0.2 95% CI: 0.08 - 0.51, p˂0.001). Also observedwere increased odds for ALL regarding male gender, mother’s high education level, mother’s freelance job, and mediumor high family income. No association with ALL incidence was observed for age, gender, breastfeeding, mother’s ageat pregnancy, malignancy in first- or second-degree relatives, or mother’s use of hair dye during pregnancy (p> 0.05).Conclusion: This study showed that father’s education level, father’s job, delivery type, birth weight, and childcarecan play a role in the incidence of childhood ALL.     

Congenital abnormalities and acute leukemia among children with Down syndrome: a Children's Oncology Group study

Children with Down syndrome, due to their heightened risk of leukemia and increased prevalence of congenital abnormalities, comprise a valuable population in which to study etiology. A Children's Oncology Group study investigated the causes of childhood leukemia in children with Down syndrome diagnosed at ages 0 to 19 years during the period 1997-2002. Telephone interviews were completed with mothers of 158 cases [n=97 acute lymphoblastic leukemia (ALL) and n=61 acute myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed via unconditional logistic regression to evaluate the association between congenital abnormalities and acute leukemia overall, and ALL and AML analyzed separately. The results do not provide evidence for an association among the index children (OR(Combined), 0.74; 95% CI, 0.45-1.23; OR(ALL), 0.67; 95% CI, 0.38-1.20; OR(AML),1.03; 95% CI, 0.49-2.16) or their siblings (OR(Combined), 1.23; 95% CI, 0.71-2.13; OR(ALL), 1.12; 95% CI, 0.60-2.09; OR(AML), 1.60; 95% CI, 0.66-3.86), suggesting congenital malformations do not confer additional risk of leukemia beyond the risk attributable to trisomy 21 in this population.     

Parental exposure to medications and hydrocarbons and ras mutations in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Ras proto-oncogene mutations have been implicated in the pathogenesis of many malignancies, including leukemia. While both human and animal studies have linked several chemical carcinogens to specific ras mutations, little data exist regarding the association of ras mutations with parental exposures and risk of childhood leukemia. Using data from a large case-control study of childhood acute lymphoblastic leukemia (ALL; age <15 years) conducted by the Children's Cancer Group, we used a case-case comparison approach to examine whether reported parental exposure to hydrocarbons at work or use of specific medications are related to ras gene mutations in the leukemia cells of children with ALL. DNA was extracted from archived bone marrow slides or cryopreserved marrow samples for 837 ALL cases. We examined mutations in K-ras and N-ras genes at codons 12, 13, and 61 by PCR and allele-specific oligonucleotide hybridization and confirmed them by DNA sequencing. We interviewed mothers and, if available, fathers by telephone to collect exposure information. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression to examine the association of parental exposures with ras mutations. A total of 127 (15.2%) cases had ras mutations (K-ras 4.7% and N-ras 10.68%). Both maternal (OR 3.2, 95% CI 1.7-6.1) and paternal (OR 2.0, 95% CI 1.1-3.7) reported use of mind-altering drugs were associated with N-ras mutations. Paternal use of amphetamines or diet pills was associated with N-ras mutations (OR 4.1, 95% CI 1.1-15.0); no association was observed with maternal use. Maternal exposure to solvents (OR 3.1, 95% CI 1.0-9.7) and plastic materials (OR 6.9, 95% CI 1.2-39.7) during pregnancy and plastic materials after pregnancy (OR 8.3, 95% CI 1.4-48.8) were related to K-ras mutation. Maternal ever exposure to oil and coal products before case diagnosis (OR 2.3, 95% CI 1.1-4.8) and during the postnatal period (OR 2.2, 95% CI 1.0-5.5) and paternal exposure to plastic materials before index pregnancy (OR 2.4, 95% CI 1.1-5.1) and other hydrocarbons during the postnatal period (OR 1.8, 95% CI 1.0-1.3) were associated with N-ras mutations. This study suggests that parental exposure to specific chemicals may be associated with distinct ras mutations in children who develop ALL.     

Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia

The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case-control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR=0.8; 95% CI (0.6-1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3-0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves' hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common ALL.     

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE)

The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first- and second-degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0-2.2]) and NHL (OR = 1.8 [1.3-2.5]), but not AL (OR = 1.0 [0.9-1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0-3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3-22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL.     

Family history of cancer and autoimmune disease and risk of leukemia in infancy: a report from the Children's Cancer Group (United States and Canada)

Objectives: As there are some suggestions that a family history of cancer or autoimmune disease might be associated with an increased risk of leukemia in children, we explored this possibility using data from a matched case-control study conducted by the Children's Cancer Group. Methods: We compared the family history of cancer and autoimmune diseases of 302 infant leukemia cases (diagnosed within the first 18 months of life) with that of 668 individually matched controls in the United States and Canada. Results: Although not significant, cancer history in parents was found to be associated with an elevated risk of infant leukemia (odds ratio [OR] = 1.4, 95 percent confidence interval [CI] = 0.6-3.6), predominantly acute myeloid leukemia (AML) (OR = 2.2, CI = 0.6-9.0). Cancer history among second-degree relatives was also related to a non-significantly elevated risk of AML. Family history of autoimmune diseases, on the other hand, was generally not found to be related to the risk of infant leukemia. Conclusion: This study provided no strong evidence that family history of cancer or autoimmune disease is a major risk factor for infant leukemia.     

Temporal patterns of association between cigarette smoking and leukemia risk

Objectives To evaluate variation in smoking-related leukemia risk with time-since-exposure. Methods We analyzed data from a population-based case–control study conducted in Germany. Odds ratios were estimated by applying conditional logistic regression methods to 470 incident leukemia cases and 1,009 controls. Cases were classified as acute non-lymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Temporal variation in the impact of smoking on leukemia risk was assessed via exposure time-windows and a spline latency function. Results Current smokers were at greater risk of ANLL than those who never smoked (OR = 1.65 95% CI: 0.95, 2.87) and a positive trend was observed in ANLL risk with cumulative pack-decades smoked, under a 2-year exposure lag assumption (OR/pack-decade = 1.11 95% CI: 0.96, 1.30). This was primarily due to the association between ANLL and smoking in the period 2 to <10 years prior (OR/pack-decade = 2.72 95% CI: 0.93, 7.99). There was minimal evidence of association between ANLL risk and packs smoked 10 or more years prior. CML and ALL exhibited minimal evidence of association with smoking status. CLL exhibited a positive association with smoking in the periods 2 to <10 years and 10 to <20 years prior to diagnosis although estimates of association were highly imprecise. Conclusions The temporal pattern of smoking-induced ANLL risk appears to follow a prompt peak in excess incidence that diminishes with time since exposure. Institute in which the work was performed: Institute for Community Medicine, Section Health Care Epidemiology and Community Health, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.     

Higher risk for acute childhood lymphoblastic leukaemia in Swedish population centres 1973-94. Swedish Child Leukaemia Group.

A population-based sample of acute childhood leukaemia cases in Sweden 1973-94 was analysed by a geographical information system (GIS) for spatial leukaemia distribution in relation to population density. The annual incidence rate for acute lymphoblastic leukaemia (ALL) was 3.6, and for acute non-lymphoblastic leukaemia (ANLL) 0.7, cases per 100,000 children. Incidence rates in population centres, constituting 1.3% of Sweden's land area and approximately 80% of the population, compared with the rest of Sweden showed a statistically significant excess of ALL [odds ratio (OR) 1.68; 95% confidence interval (CI) 1.44-1.95], but not ANLL (OR 1.13; 95% CI 0.98-1.32). An increasing trend, however not statistically significant, was found for ALL incidence with both increasing population density in parishes and increasing degree of urbanity in municipalities. These findings support the theories that some environmental factors associated with high population density, such as infectious agents, may be of aetiological importance for childhood acute lymphoblastic leukaemia.     

Birth weight and childhood leukemia: A meta‐analysis and review of the current evidence

A growing body of evidence suggests that childhood leukemia may be initiated in utero when lymphoid and myeloid cells are not fully differentiated and are particularly susceptible to malignant transformation. A fixed effects meta‐analysis examining the association between birth weight and childhood leukemia was conducted including 32 studies and 16,501 cases of all types of leukemia (OL), 10,974 cases of acute lymphoblastic leukemia (ALL), and 1,832 cases of acute myeloid leukemia (AML). The odd ratios (OR) for the association of high birth weight with OL, ALL and AML were 1.35 (95% CI: 1.24, 1.48), 1.23 (95% CI: 1.15, 1.32), and 1.40 (95% CI: 1.11, 1.76), respectively, compared with normal birth weight. Low birth weight was not associated with overall and ALL leukemia, but with AML (OR = 1.50; 95% CI: 1.05, 2.13). Per 1000 g increase in birth weight, the OR for OL was 1.18 (95% CI: 1.13, 1.23) and ALL 1.18 (95% CI: 1.12, 1.23). The combined available evidence from observational studies suggests that high birth weight is associated with an increased risk of overall leukemia and ALL. For AML the risk may be elevated at both high and low extremes of birth weight, suggesting a U‐shaped association. © 2008 Wiley‐Liss, Inc.     

Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia

INTRODUCTION: We investigated the role of maternal alcohol and coffee drinking and parental smoking on the risk of childhood acute leukemia in a multicenter case-control study. METHODS: The study included 280 incident cases and 288 hospitalized controls, frequency matched with the cases by age, gender and center. Data collection was completed by face-to-face standardized interviews of the case and control mothers. RESULTS: An association with maternal alcohol consumption during pregnancy was observed with acute lymphoid leukemia (ALL) (OR=2.0 [1.4-3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2-5.8]). Maternal coffee consumption during pregnancy was associated with childhood acute leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7-1.8], OR=2.4 [1.3-4.7] and OR=3.1 [1.0-9.5], respectively, for < or =3, 4-8 and >8 cups/day). No association with maternal smoking during pregnancy or parental smoking before or after the index child's birth was observed. DISCUSSION: Our results suggest an association with maternal alcohol and coffee drinking during pregnancy and call for further investigations. Besides, the present study does not support the hypothesis of an increase in the risk of childhood leukemia related to parental smoking.     

Atopic disease and childhood acute lymphoblastic leukemia

Our objective was to test the hypothesis that the risk of childhood leukemia is associated with allergies or a family history of allergy. We used a German population-based case-control study with self-reported information on allergies of the children and their first-degree relatives. Our study included a total of 1,130 cases of acute lymphoblastic leukemia (ALL), 164 cases of acute myeloid leukemia (AML) and 2,957 controls. A major finding of our study is that hay fever, neurodermatitis and contact eczema are underrepresented within the group of children with ALL, with respective odds ratios (OR) of 0.45 (95% confidence interval [CI] 0.31-0.66) for hay fever, of 0.49 (CI 0.34-0.71) for neurodermatitis and of 0.62 (CI 0.39-0.99) for eczema, respectively. Atopic diseases, comprising hay fever, neurodermatitis and asthma, are much stronger related with a reduced risk of ALL than other allergies (OR 0.52, CI 0.40-0.67 vs. OR 0.89, CI 0.66-1.21). The strongest association is seen with an atopy in the index child; however, ALL risk is also reduced if one of the parents or a sibling had an atopic disease. No such consistent pattern is seen for AML. Our data suggest that atopy or a family history of atopy are associated with a reduced risk of childhood ALL. Recall bias remains a concern, but sensitivity analysis provided some evidence that the protective effect is unlikely to be attributable to this bias in its entirety.     

Parental cigarette smoking and the risk of acute leukemia in children

BACKGROUND: Studies of the relation between parental smoking and childhood leukemia have produced inconsistent results. In the largest case-control studies of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) conducted to date, the authors evaluated leukemia risk relative to parental self-report of cigarette smoking. METHODS: In telephone interviews in which a structured questionnaire was used, parents of 1842 ALL patients, 517 AML patients, and their matched controls were asked about their cigarette smoking habits before, during, and after the pregnancy with the index child. Risk of leukemia was examined by histologic type, age of the child at diagnosis, immunophenotype (for ALL), and French-American-British morphology group (for AML). RESULTS: The risk of ALL was not associated with the father's ever having smoked (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.90-1.20) or the mother's ever having smoked (OR = 1.04, 95% CI 0.91-1.19). Similarly, no significant risk of AML was observed for paternal (OR = 0.88, 95% CI 0.67-1.16) or maternal smoking (OR = 0.95, 95% CI 0.74-1.22). The relative risk of leukemia was not significantly different from the null for parental smoking in any time period during or around the index pregnancy, nor was it related to the number of cigarettes, the number of years of smoking, or the number of pack-years. A small number of sporadic, statistically significant associations were found, but overall there appeared to be no association between parental cigarette smoking and ALL or AML, or any subgroup of leukemia. CONCLUSIONS: Parental smoking while pregnant or exposure to cigarette smoke shortly after birth is unlikely to contribute substantially to the risk of childhood leukemia in North America.     

Birth characteristics, maternal reproductive history, hormone use during pregnancy, and risk of childhood acute lymphocytic leukemia by immunophenotype (United States)

Objective: To investigate the associations of birth characteristics and maternal reproductive factors with risk of childhood acute lymphoblastic leukemia (ALL) by immunophenotypic subtypes. Methods: Data collected from a case–control study including 1842 ALL cases (age < 15 years) and 1986 individually matched controls were analyzed. Exposure information was obtained through telephone interviews of parents. Results: Factors associated with risk of ALL from all subgroups combined included high birth weight (OR = 1.4, 95% CI = 1.1–1.8), high birth order (OR = 2.0, 95% CI = 1.3–3.0 for fourth-born child compared to first-born child), young maternal age (<20 compared to 25–29, OR = 1.4, 95% CI = 1.1–1.9), advanced paternal age ( > 39 compared to 25–29, OR = 1.4, 95% CI = 1.0–1.9), induced abortion prior to the index pregnancy (OR = 1.2, 95% CI = 1.0–1.4), and oral contraceptive use during the index pregnancy (OR = 1.5, 95% CI = 1.0–2.2) with children under the age of 2 (OR = 5.1, 95% CI = 1.0–24.7) being the predominantly affected group. Risk of early pre-B-cell ALL increased with advanced paternal age (OR = 1.7, 95% CI = 1.1–2.7) and high birth order (OR = 2.0, 95% CI = 1.1–3.6), while risk of pre-B-cell ALL increased with both younger (OR = 3.4, 95% CI = 1.4–8.4) and advanced maternal age (OR = 2.6, 95% CI = 1.1–5.9). T-cell ALL was associated with high birth weight (OR = 2.4, 95% CI = 1.1–5.5) and history of induced abortion (OR = 2.4, 95% CI = 1.3–4.5). Conclusion: This study suggests that the association of ALL with birth characteristics and maternal reproductive factors varies with the immunophenotype of the ALL. Future studies are needed to better understand the effect of maternal hormone in the development of subtype of childhood ALL.     

Breast-feeding and risk of childhood acute leukemia.

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.