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.     

Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study

Objective As part of a larger case–control study, the authors evaluated risk of childhood leukemia relative to parental self-reported smoking and alcohol consumption. Methods Children 0–14 years of age diagnosed with leukemia between 1990 and 1994 were ascertained through population-based sources at the time of diagnosis. For each participating case, an age, gender, and area-matched control was randomly selected from provincial government health insurance rolls. Risk factor information was obtained through personal interviews with each child’s parents. Conditional logistic regression models were used to examine risk of leukemia associated with parental smoking and drinking. Results Maternal alcohol consumption prior to conception (OR = 1.37, 95% CI, 0.99–1.90) and during pregnancy (OR = 1.39, 95% CI, 1.01–1.93) was associated with an excess risk of childhood leukemia, with a positive dose-response trend for increasing weekly consumption (p < 0.05). Similar results were observed for children diagnosed with acute lymphoblastic leukemia (ALL). Odds ratios for maternal cigarette smoking before and during pregnancy were consistently elevated above one, but not statistically significant. No relationship was observed with paternal drinking or smoking in the perinatal period. Conclusions Our study suggests that maternal alcohol drinking before or during pregnancy may contribute to an increased risk of childhood leukemia.     

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.     

Risk of childhood germ cell tumors in association with parental smoking and drinking

BACKGROUND: The etiology of childhood germ cell tumors (GCT) is not well understood. The Children's Oncology Group conducted the largest case-control study of childhood GCT to investigate whether parental exposures to smoking and alcohol contributed to the disease. METHODS: Cases included 274 children with GCT diagnosed between January 1, 1993 and December 31, 2001 who were age <15 years. Controls (n=421) were selected by random digit dialing and were frequency matched based on gender, age (+/-1 year), and geographic area. Exposure information was collected from subjects' parents using independent telephone interviews and self-administrated questionnaires. RESULTS: No association was found between parental smoking or drinking alcohol and risk of childhood GCT (for smoking: odds ratio [OR]=1.0, 95% confidence interval [95% CI], 0.8-1.3 and OR = 1.2, 95% CI, 0.9-1.5, for mothers and fathers, respectively; for drinking: OR=0.9, 95% CI, 0.7-1.2 and OR=1.0, 95% CI, 0.8-1.3, for mothers and fathers, respectively). No significant trend was observed for length of maternal exposure to passive smoking during the index pregnancy and GCT risk (for total subject: P=0.77; boys: P=0.52; girls: P=0.93). CONCLUSIONS: The authors found no evidence that childhood GCT was related to prenatal exposure to parental cigarette smoking, alcohol drinking, and maternal passive smoking.     

Parental medication use and risk of childhood acute lymphoblastic leukemia

BACKGROUND: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. METHODS: Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 individually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. RESULTS: After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of amphetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for amphetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. CONCLUSIONS: The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring.     

Parental smoking and alcohol consumption and risk of neuroblastoma.

Previous studies and animal evidence have suggested a relationship between parental tobacco or alcohol use and the risk of some childhood cancers, including neuroblastoma. A case-control study was conducted to investigate the relationship between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma. Cases were children diagnosed with neuroblastoma over the period 1992-1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected using random-digit dialing. Information on parental smoking and drinking history was obtained from 504 case and 504 control parents by telephone interview. Overall, there was no consistent pattern of association with parental smoking and alcohol consumption. For example, both maternal smoking and drinking during the period from 1 month before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95% confidence interval (CI), 0.8-1.4]. There was no association with paternal smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception (OR, 1.0; 95% CI, 0.7-1.4). There was no consistent increase in risk by the amount of smoking or drinking during any time period relative to pregnancy. There was no suggestion of an increased risk when only one parent smoked. Smoking or drinking among both parents did not jointly increase the risk of neuroblastoma in their offspring. The child's age at diagnosis, stage, or MYCN oncogene amplification status did not materially alter the OR estimates. It is concluded that the results from this study do not indicate any evidence for a relationship between neuroblastoma and parental tobacco or alcohol use.     

Childhood hematopoietic malignancies and parental use of tobacco and alcohol: the ESCALE study (SFCE)

Objectives

Investigating the role of parental smoking and maternal alcohol consumption in the etiology of childhood hematopoietic malignancies.

Methods

The national registry-based case–control study ESCALE was carried out in France over the period 2003–2004. Population controls were frequency matched with the cases on age and gender. Maternal smoking and alcohol consumption during pregnancy and paternal smoking since before conception were reported by the mothers in a structured telephone questionnaire. Odds ratios (OR) were estimated using unconditional regression models closely adjusted for potential confounders.

Results

A total of 765 cases of acute leukemia (AL), 130 of Hodgkin’s lymphoma (HL), 165 of non-Hodgkin’s lymphoma (NHL) and 1681 controls were included. Paternal smoking was significantly associated with childhood ALL (OR = 1.4 [1.1–1.7]), AML (OR = 1.5 [1.0–2.3]), Burkitt (OR = 2.0 [1.2–3.2]), and anaplastic large cell (OR = 3.2 [1.2–9.1]) NHL. For the four diseases, the ORs significantly increased with the number of cigarettes smoked. No association with HL or with other types of NHL was observed. The associations with maternal alcohol consumption and cigarette smoking during pregnancy were less consistent.

Conclusion

The results support the hypothesis that only paternal smoking, and not maternal alcohol consumption or cigarette smoking, plays a role in childhood hematopoietic malignancies.     

Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy.

Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene-environment interactions were estimated using both case-control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and 0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.     

Parental smoking,maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies

Neuroblastoma (NB) is the most common extra-cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population-based case–control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life-style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta-analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9–1.7]; summary OR from meta-analysis 1.1 [95% CI 1.0–1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9–1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1–2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8–1.4], summary OR from meta-analysis 1.0 [95% CI 0.9–1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy.     

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.     

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.     

Childhood acute leukemia, maternal beverage intake during pregnancy, and metabolic polymorphisms

Purpose

This study aimed to analyze the associations between childhood acute leukemia (AL) and maternal caffeinated beverage consumption during pregnancy, and to explore interactions between caffeinated and alcoholic beverage consumption and polymorphisms of enzymes involved in caffeine and ethanol metabolisms.

Methods

The data were generated by the French ESCALE study, which included 764 AL cases and 1,681 controls in 2003–2004. The case and control mothers were interviewed on their consumption habits during pregnancy using a standardized questionnaire. Genotypes of the candidate alleles (NAT2*5 rs1801280, ADH1C*2 rs698 and rs1693482, CYP2E1*5 rs2031920 and rs3813867) were obtained using high-throughput genotyping and imputation data for 493 AL cases and 549 controls with at least two grandparents born in Europe.

Results

Maternal regular coffee consumption during pregnancy was associated with childhood AL (OR = 1.2 [1.0–1.5], p = 0.02); the odds ratios increased linearly with daily intake (p for trend <0.001; >2 cups per day vs. no or less than 1 cup per week: AL: OR = 1.6 [1.2–2.1], lymphoblastic AL: OR = 1.5 [1.1–2.0], myeloblastic AL: OR = 2.4 [1.3–4.3]). The association was slightly more marked for children born to non-smoking mothers. Lymphoblastic AL was also associated with cola soda drinking (OR = 1.3 [1.0–1.5], p = 0.02). No significant gene–environment interactions with coffee, tea, cola soda, or alcohol drinking were observed.

Conclusion

This study provides additional evidence that maternal coffee consumption during pregnancy may be associated with childhood AL. Coffee consumption is a prevalent habit and its potential involvement in childhood AL needs to be considered further.     

Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: results from an Australian case?Ccontrol study

Objectives

To investigate whether maternal coffee and/or tea consumption during the last 6?months of pregnancy was associated with risk of childhood ALL.

Methods

Data on coffee and tea drinking during pregnancy from 337 case mothers and 697 control mothers were analyzed using unconditional multivariable logistic regression. A meta-analysis of our findings with those of previous studies was also conducted.

Results

There was little evidence of an overall association between maternal coffee consumption and risk of ALL: OR 0.89 (95% CI 0.61, 1.30), although there was some suggestion that higher levels of intake might increase the risk in children of non-smoking mothers: OR for 2+ cups/day?=?1.44 (95% CI 0.85, 2.42); this was supported by our meta-analysis. Risk was also elevated among cases with chromosomal translocations. The overall OR for maternal tea consumption was 0.82 (95% CI 0.56, 1.18), although the OR for T-cell ALL was 0.21 (95% CI 0.08, 0.51). Among ALL cases with translocations, the ORs for tea consumption tended to be elevated: OR?=?1.70 (95% CI 0.79?C3.68) for 2+ cups/day.

Conclusions

The observed increased risk associated with coffee and tea consumption may be confined to ALL with translocations. These associations should be explored further in large international consortia.     

Medical and drug risk factors associated with neuroblastoma: a case-control study

A matched case-control study of prenatal risk factors for neuroblastoma was conducted, including 104 cases diagnosed over the period 1970-79 in the Greater Delaware Valley. Significantly elevated odds ratios (ORs) were associated with maternal use of a neurally active drug during pregnancy (OR = 2.83), sex hormone exposure 3 months prior to or during pregnancy (OR = 2.25), frequent alcohol consumption during pregnancy (OR = 9.0), and maternal use of diuretic drugs during pregnancy (OR = 5.75). Significantly more case mothers than control mothers reported use of hair coloring products during pregnancy (OR = 3.0). No association was found between cigarette smoking, coffee consumption, or medical irradiation and case-control status.     

Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case–control study

Purpose

Tobacco smoke could cause childhood acute lymphoblastic leukemia (ALL) through at least three pathways: (1) prenatal parental smoking; (2) fetal exposure through maternal smoking during pregnancy; and (3) childhood exposure to secondhand smoke (SHS). We tested these hypotheses in a large population-based case–control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood hematopoietic malignancies.

Methods

From 1998 to 2003, we enrolled 602 incident cases of ALL from 14 Italian Regions, and 918 controls were individually matched by birthdate, sex, and area of residence. Cases (n = 557) and controls (n = 855) with complete information were analyzed; odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated with logistic regression models conditioned on matching variables and adjusted by birth order, birthweight, duration of breastfeeding, parental age at delivery, education, and occupational exposure to benzene.

Results

No evidence associating paternal smoking in the conception period or maternal smoking during the pregnancy with ALL was found. An association of ALL with maternal exposure to SHS during pregnancy (adjusted OR for mothers exposed more than 4 h/day = 2.18, 95 % CI 1.39–3.42) was observed, but recall bias cannot be excluded. Exposure of the children to SHS was associated with ALL only in unadjusted analysis (unadjusted OR for highly exposed children = 1.64; 95 % CI 1.10–2.45).

Conclusions

This study does not support the hypothesis that parental active smoking is associated with ALL. We found very weak evidence of increased risk of ALL for children exposed to SHS. Maternal exposure to SHS was associated with ALL, but recall bias is likely to inflate our estimates.     

Parental smoking,maternal alcohol,coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE,France)

Purpose

To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT.

Methods

We pooled data from two French national population-based case–control studies with similar designs conducted in 2003–2004 and 2010–2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin.

Results

No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74).

Conclusion

We found some evidence of a weak association between paternal smoking in the year before the child’s birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes.

     

Parental occupation and other environmental factors in the etiology of leukemias and non-Hodgkin's lymphomas in childhood: a case-control study

We report the results of a hospital-based, case-control study on acute lymphocytic leukemia (ALL), acute non-lymphocytic leukemia (AnLL) and non-Hodgkin lymphoma (NHL) in childhood. The study was conducted from 1981 to 1984 in Turin (Italy). One hundred and forty-two children with ALL, 22 with AnLL and 19 with NHL were included, as well as 307 controls. Information on parental smoking habits, parental occupation, ionizing radiation and childhood diseases were collected using a standard questionnaire during a personal interview of the relative attending the child in the hospital. The odds ratios for antenatal diagnostic radiation were 1.1 (NS) for ALL and 2.4 (NS) for AnLL. No association was found with diseases in childhood. Paternal and maternal smoking habits were similar for ALL cases and controls. Both maternal and paternal smoking were associated with NHL: for paternal smoking, odds ratios were around 5, but without a correlation with number of cigarettes. Positive associations observed with maternal employment were: ALL with teacher and cleaner; AnLL and textile worker; NHL and baker. Corresponding association with paternal jobs were: ALL with clerks, farmers and employment in office equipment production; AnLL and workers in building, tire or textile industries; NHL and lorry drivers, workers in the building or in the wood and furniture industry.     

Maternal Pregnancy Loss,Birth Characteristics,and Childhood Leukemia (United States)

Objective: The authors evaluated the relation between maternal pregnancy loss, birth characteristics, and childhood leukemia in the Northern California Childhood Leukemia Study. Methods: Incident cases of childhood leukemia (age 0–14 years) were rapidly ascertained, and controls were randomly selected from birth records and individually matched to cases. A total of 366 cases [313 acute lymphoblastic leukemia (ALL) and 53 acute myeloid leukemia (AML)] and 460 controls were included in this analysis. The biological mothers of all subjects provided detailed reproductive history and birth characteristics of the index children during a personal interview. Odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Data on maternal pregnancy loss and birth characteristics were also available from the birth certificates of 96.3% of all subjects. Results: History of miscarriage was associated with a significantly increased risk of AML (OR = 2.94, 95% CI: 1.03, 8.34), but not ALL. Neither birth weight, birth order, or parental ages appeared to be an important predictor of the risk of ALL or AML. A comparison between data from two different sources (interview versus birth certificate) indicated good reproducibility and offered some evidence against recall bias. Conclusion: Maternal history of miscarriage is associated with an increased risk of childhood AML.     

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.     

Maternal smoking and childhood leukemia and lymphoma risk among 1,440,542 Swedish children.

Possible in utero effects of maternal smoking on hemopoietic cancer in the offspring have been addressed previously, although the results are inconclusive. In this investigation, we take advantage of population-based registers in Sweden to examine maternal smoking during pregnancy and childhood risk of leukemia and lymphoma. Prospective data were available from 1,440,542 Swedish children born between 1983 and 1997. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) controlling for potential confounders. In the study base, 750 hemopoietic cancers occurred across 11 million person-years. Incidence rates per 100,000 person-years were 4.7 for acute lymphocytic leukemia (ALL), 0.45 for acute myelogenous leukemia, and 0.76 for non-Hodgkin's lymphoma. Maternal smoking was associated with a lower risk of ALL (HR, 0.73; 95% CI, 0.58-0.91). On the other hand, there was a higher risk of acute myelogenous leukemia (HR, 1.41; 95% CI, 0.74-2.67) particularly among heavy (> or =10 cigarettes per day) smokers (HR, 2.28; 95% CI, 1.05-4.94). The data also suggested a small excess risk of non-Hodgkin's lymphoma (HR, 1.25; 95% CI, 0.76-2.04). Evidence from this large cohort suggests that maternal smoking affects the risk of childhood leukemia and lymphoma in the offspring. The Swedish registries provide unique opportunities to examine this research question, with a design inherently free of selection and recall biases. The apparent protective effect with ALL needs to be explored further and in no way supports maternal smoking as beneficial, given its adverse association with common pregnancy outcomes.